PMC:1064873 / 14998-17327
Annnotations
LappsTest
{"project":"LappsTest","denotations":[{"id":"T12196","span":{"begin":1850,"end":1854},"obj":"Protein"},{"id":"T12195","span":{"begin":1801,"end":1805},"obj":"Protein"},{"id":"T12194","span":{"begin":1779,"end":1784},"obj":"Protein"},{"id":"T12193","span":{"begin":1683,"end":1687},"obj":"Protein"},{"id":"T12192","span":{"begin":1423,"end":1428},"obj":"Protein"},{"id":"T12191","span":{"begin":1221,"end":1224},"obj":"Protein"},{"id":"T12190","span":{"begin":1164,"end":1167},"obj":"Protein"},{"id":"T12189","span":{"begin":1019,"end":1023},"obj":"Protein"},{"id":"T12188","span":{"begin":932,"end":937},"obj":"Protein"},{"id":"T12187","span":{"begin":878,"end":883},"obj":"Protein"},{"id":"T12186","span":{"begin":785,"end":792},"obj":"Protein"},{"id":"T12185","span":{"begin":699,"end":703},"obj":"Protein"},{"id":"T12184","span":{"begin":483,"end":535},"obj":"Protein"},{"id":"T12183","span":{"begin":381,"end":388},"obj":"Protein"},{"id":"T12182","span":{"begin":365,"end":370},"obj":"Protein"},{"id":"T12181","span":{"begin":346,"end":353},"obj":"Protein"},{"id":"T12180","span":{"begin":276,"end":305},"obj":"Protein"},{"id":"T12179","span":{"begin":231,"end":235},"obj":"Protein"},{"id":"T12178","span":{"begin":175,"end":180},"obj":"Protein"},{"id":"T12177","span":{"begin":74,"end":100},"obj":"Protein"},{"id":"T12176","span":{"begin":54,"end":61},"obj":"Protein"},{"id":"T12175","span":{"begin":14,"end":19},"obj":"Protein"},{"id":"T12201","span":{"begin":2299,"end":2304},"obj":"Protein"},{"id":"T12200","span":{"begin":2225,"end":2232},"obj":"Protein"},{"id":"T12199","span":{"begin":1998,"end":2002},"obj":"Protein"},{"id":"T12198","span":{"begin":1934,"end":1939},"obj":"Protein"},{"id":"T12197","span":{"begin":1869,"end":1873},"obj":"Protein"}],"text":"Resistance to IL-10 inhibition of IFN-γ production in RA CD4+ T cells\nThe CD28 costimulatory pathway is crucial for effective antigen-specific T-cell cytokine production, and IL-10 can directly suppress this response by inhibiting CD28 tyrosine phosphorylation and binding of phosphatidylinositol 3-kinase [24]. To evaluate the responsiveness of RA CD4+ T cells to IL-10, purified PB CD4+ T cells from three patients with active RA and from three healthy controls were stimulated by immobilized anti-CD3 antibody and anti-CD28 antibody with or without diluted concentrations of IL-10 for 36 hours, and IFN-γ production was measured by ELISA. As shown in Fig. 1, IFN-γ production by activated normal CD4+ T cells was mostly inhibited at concentrations as low as 1 ng/ml IL-10. However, RA CD4+ T cells were able to produce significant amounts of IFN-γ in the presence of 1 ng/ml IL-10, and the maximal but not complete inhibition by IL-10 was obtained at 10–100 ng/ml.\nWe thus compared the levels of IFN-γ production by CD4+ T cells after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 in RA patients with active disease (multiple inflammatory joints, CRP level ≥ 10 mg/l) and inactive disease (in remission, CRP level \u003c 10 mg/l) [26] and in healthy controls. There were no statistically significant differences in IFN-γ production without IL-10 among these three groups (Fig. 2a), but the inhibitory effect of IL-10 on IFN-γ production was significantly limited in the active RA group as compared with the inactive RA group and healthy controls (percentage decrease: active RA, 2.9 ± 14.4%; inactive RA, 45.6 ± 14.4%; controls, 65.8 ± 7.9%) (Fig. 2b). As a consequence, CD4+ T cells from active RA patients produced higher levels of IFN-γ in the presence of 1 ng/ml IL-10 than did normal CD4+ T cells (Fig. 2a).\nIn addition, we compared IL-2 production by CD4+ T cells after CD3 and CD28 costimulation in the presence of IL-10 in active RA patients and in healthy controls. Similarly, IL-2 production was not affected by 1 ng/ml IL-10 in RA patients (percentage decrease, -2.1 ± 13.8%), while it was significantly reduced in healthy controls (61.1 ± 13.7%; P \u003c 0.05). Taken together, these results indicate that RA CD4+ T cells become less susceptible to the immunoregulatory effect of IL-10 during the active phase."}
2_test
{"project":"2_test","denotations":[{"id":"15535835-10898505-4156888","span":{"begin":307,"end":309},"obj":"10898505"},{"id":"15535835-7306232-4156889","span":{"begin":1243,"end":1245},"obj":"7306232"}],"text":"Resistance to IL-10 inhibition of IFN-γ production in RA CD4+ T cells\nThe CD28 costimulatory pathway is crucial for effective antigen-specific T-cell cytokine production, and IL-10 can directly suppress this response by inhibiting CD28 tyrosine phosphorylation and binding of phosphatidylinositol 3-kinase [24]. To evaluate the responsiveness of RA CD4+ T cells to IL-10, purified PB CD4+ T cells from three patients with active RA and from three healthy controls were stimulated by immobilized anti-CD3 antibody and anti-CD28 antibody with or without diluted concentrations of IL-10 for 36 hours, and IFN-γ production was measured by ELISA. As shown in Fig. 1, IFN-γ production by activated normal CD4+ T cells was mostly inhibited at concentrations as low as 1 ng/ml IL-10. However, RA CD4+ T cells were able to produce significant amounts of IFN-γ in the presence of 1 ng/ml IL-10, and the maximal but not complete inhibition by IL-10 was obtained at 10–100 ng/ml.\nWe thus compared the levels of IFN-γ production by CD4+ T cells after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 in RA patients with active disease (multiple inflammatory joints, CRP level ≥ 10 mg/l) and inactive disease (in remission, CRP level \u003c 10 mg/l) [26] and in healthy controls. There were no statistically significant differences in IFN-γ production without IL-10 among these three groups (Fig. 2a), but the inhibitory effect of IL-10 on IFN-γ production was significantly limited in the active RA group as compared with the inactive RA group and healthy controls (percentage decrease: active RA, 2.9 ± 14.4%; inactive RA, 45.6 ± 14.4%; controls, 65.8 ± 7.9%) (Fig. 2b). As a consequence, CD4+ T cells from active RA patients produced higher levels of IFN-γ in the presence of 1 ng/ml IL-10 than did normal CD4+ T cells (Fig. 2a).\nIn addition, we compared IL-2 production by CD4+ T cells after CD3 and CD28 costimulation in the presence of IL-10 in active RA patients and in healthy controls. Similarly, IL-2 production was not affected by 1 ng/ml IL-10 in RA patients (percentage decrease, -2.1 ± 13.8%), while it was significantly reduced in healthy controls (61.1 ± 13.7%; P \u003c 0.05). Taken together, these results indicate that RA CD4+ T cells become less susceptible to the immunoregulatory effect of IL-10 during the active phase."}
biosemtest
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to IL-10 inhibition of IFN-γ production in RA CD4+ T cells\nThe CD28 costimulatory pathway is crucial for effective antigen-specific T-cell cytokine production, and IL-10 can directly suppress this response by inhibiting CD28 tyrosine phosphorylation and binding of phosphatidylinositol 3-kinase [24]. To evaluate the responsiveness of RA CD4+ T cells to IL-10, purified PB CD4+ T cells from three patients with active RA and from three healthy controls were stimulated by immobilized anti-CD3 antibody and anti-CD28 antibody with or without diluted concentrations of IL-10 for 36 hours, and IFN-γ production was measured by ELISA. As shown in Fig. 1, IFN-γ production by activated normal CD4+ T cells was mostly inhibited at concentrations as low as 1 ng/ml IL-10. However, RA CD4+ T cells were able to produce significant amounts of IFN-γ in the presence of 1 ng/ml IL-10, and the maximal but not complete inhibition by IL-10 was obtained at 10–100 ng/ml.\nWe thus compared the levels of IFN-γ production by CD4+ T cells after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 in RA patients with active disease (multiple inflammatory joints, CRP level ≥ 10 mg/l) and inactive disease (in remission, CRP level \u003c 10 mg/l) [26] and in healthy controls. There were no statistically significant differences in IFN-γ production without IL-10 among these three groups (Fig. 2a), but the inhibitory effect of IL-10 on IFN-γ production was significantly limited in the active RA group as compared with the inactive RA group and healthy controls (percentage decrease: active RA, 2.9 ± 14.4%; inactive RA, 45.6 ± 14.4%; controls, 65.8 ± 7.9%) (Fig. 2b). As a consequence, CD4+ T cells from active RA patients produced higher levels of IFN-γ in the presence of 1 ng/ml IL-10 than did normal CD4+ T cells (Fig. 2a).\nIn addition, we compared IL-2 production by CD4+ T cells after CD3 and CD28 costimulation in the presence of IL-10 in active RA patients and in healthy controls. Similarly, IL-2 production was not affected by 1 ng/ml IL-10 in RA patients (percentage decrease, -2.1 ± 13.8%), while it was significantly reduced in healthy controls (61.1 ± 13.7%; P \u003c 0.05). 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to IL-10 inhibition of IFN-γ production in RA CD4+ T cells\nThe CD28 costimulatory pathway is crucial for effective antigen-specific T-cell cytokine production, and IL-10 can directly suppress this response by inhibiting CD28 tyrosine phosphorylation and binding of phosphatidylinositol 3-kinase [24]. To evaluate the responsiveness of RA CD4+ T cells to IL-10, purified PB CD4+ T cells from three patients with active RA and from three healthy controls were stimulated by immobilized anti-CD3 antibody and anti-CD28 antibody with or without diluted concentrations of IL-10 for 36 hours, and IFN-γ production was measured by ELISA. As shown in Fig. 1, IFN-γ production by activated normal CD4+ T cells was mostly inhibited at concentrations as low as 1 ng/ml IL-10. However, RA CD4+ T cells were able to produce significant amounts of IFN-γ in the presence of 1 ng/ml IL-10, and the maximal but not complete inhibition by IL-10 was obtained at 10–100 ng/ml.\nWe thus compared the levels of IFN-γ production by CD4+ T cells after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 in RA patients with active disease (multiple inflammatory joints, CRP level ≥ 10 mg/l) and inactive disease (in remission, CRP level \u003c 10 mg/l) [26] and in healthy controls. There were no statistically significant differences in IFN-γ production without IL-10 among these three groups (Fig. 2a), but the inhibitory effect of IL-10 on IFN-γ production was significantly limited in the active RA group as compared with the inactive RA group and healthy controls (percentage decrease: active RA, 2.9 ± 14.4%; inactive RA, 45.6 ± 14.4%; controls, 65.8 ± 7.9%) (Fig. 2b). As a consequence, CD4+ T cells from active RA patients produced higher levels of IFN-γ in the presence of 1 ng/ml IL-10 than did normal CD4+ T cells (Fig. 2a).\nIn addition, we compared IL-2 production by CD4+ T cells after CD3 and CD28 costimulation in the presence of IL-10 in active RA patients and in healthy controls. Similarly, IL-2 production was not affected by 1 ng/ml IL-10 in RA patients (percentage decrease, -2.1 ± 13.8%), while it was significantly reduced in healthy controls (61.1 ± 13.7%; P \u003c 0.05). Taken together, these results indicate that RA CD4+ T cells become less susceptible to the immunoregulatory effect of IL-10 during the active phase."}
bionlp-st-ge-2016-test-proteins
{"project":"bionlp-st-ge-2016-test-proteins","denotations":[{"id":"T12929","span":{"begin":2299,"end":2304},"obj":"Protein"},{"id":"T12913","span":{"begin":1092,"end":1097},"obj":"Protein"},{"id":"T12912","span":{"begin":1046,"end":1050},"obj":"Protein"},{"id":"T12911","span":{"begin":1038,"end":1041},"obj":"Protein"},{"id":"T12910","span":{"begin":1019,"end":1022},"obj":"Protein"},{"id":"T12909","span":{"begin":999,"end":1004},"obj":"Protein"},{"id":"T12908","span":{"begin":932,"end":937},"obj":"Protein"},{"id":"T12907","span":{"begin":878,"end":883},"obj":"Protein"},{"id":"T12906","span":{"begin":845,"end":850},"obj":"Protein"},{"id":"T12905","span":{"begin":788,"end":791},"obj":"Protein"},{"id":"T12904","span":{"begin":769,"end":774},"obj":"Protein"},{"id":"T12903","span":{"begin":699,"end":702},"obj":"Protein"},{"id":"T12902","span":{"begin":662,"end":667},"obj":"Protein"},{"id":"T12901","span":{"begin":602,"end":607},"obj":"Protein"},{"id":"T12900","span":{"begin":578,"end":583},"obj":"Protein"},{"id":"T12899","span":{"begin":522,"end":526},"obj":"Protein"},{"id":"T12898","span":{"begin":500,"end":503},"obj":"Protein"},{"id":"T12897","span":{"begin":384,"end":387},"obj":"Protein"},{"id":"T12896","span":{"begin":365,"end":370},"obj":"Protein"},{"id":"T12895","span":{"begin":349,"end":352},"obj":"Protein"},{"id":"T12894","span":{"begin":231,"end":235},"obj":"Protein"},{"id":"T12893","span":{"begin":175,"end":180},"obj":"Protein"},{"id":"T12892","span":{"begin":74,"end":78},"obj":"Protein"},{"id":"T12891","span":{"begin":57,"end":60},"obj":"Protein"},{"id":"T12890","span":{"begin":34,"end":39},"obj":"Protein"},{"id":"T12889","span":{"begin":14,"end":19},"obj":"Protein"},{"id":"T12928","span":{"begin":2228,"end":2231},"obj":"Protein"},{"id":"T12927","span":{"begin":2042,"end":2047},"obj":"Protein"},{"id":"T12926","span":{"begin":1998,"end":2002},"obj":"Protein"},{"id":"T12925","span":{"begin":1934,"end":1939},"obj":"Protein"},{"id":"T12924","span":{"begin":1896,"end":1900},"obj":"Protein"},{"id":"T12923","span":{"begin":1869,"end":1872},"obj":"Protein"},{"id":"T12922","span":{"begin":1850,"end":1854},"obj":"Protein"},{"id":"T12921","span":{"begin":1801,"end":1804},"obj":"Protein"},{"id":"T12920","span":{"begin":1779,"end":1784},"obj":"Protein"},{"id":"T12919","span":{"begin":1746,"end":1751},"obj":"Protein"},{"id":"T12918","span":{"begin":1683,"end":1686},"obj":"Protein"},{"id":"T12917","span":{"begin":1432,"end":1437},"obj":"Protein"},{"id":"T12916","span":{"begin":1423,"end":1428},"obj":"Protein"},{"id":"T12915","span":{"begin":1352,"end":1357},"obj":"Protein"},{"id":"T12914","span":{"begin":1327,"end":1332},"obj":"Protein"}],"namespaces":[{"prefix":"_base","uri":"http://bionlp.dbcls.jp/ontology/ge.owl#"}],"text":"Resistance to IL-10 inhibition of IFN-γ production in RA CD4+ T cells\nThe CD28 costimulatory pathway is crucial for effective antigen-specific T-cell cytokine production, and IL-10 can directly suppress this response by inhibiting CD28 tyrosine phosphorylation and binding of phosphatidylinositol 3-kinase [24]. To evaluate the responsiveness of RA CD4+ T cells to IL-10, purified PB CD4+ T cells from three patients with active RA and from three healthy controls were stimulated by immobilized anti-CD3 antibody and anti-CD28 antibody with or without diluted concentrations of IL-10 for 36 hours, and IFN-γ production was measured by ELISA. As shown in Fig. 1, IFN-γ production by activated normal CD4+ T cells was mostly inhibited at concentrations as low as 1 ng/ml IL-10. However, RA CD4+ T cells were able to produce significant amounts of IFN-γ in the presence of 1 ng/ml IL-10, and the maximal but not complete inhibition by IL-10 was obtained at 10–100 ng/ml.\nWe thus compared the levels of IFN-γ production by CD4+ T cells after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 in RA patients with active disease (multiple inflammatory joints, CRP level ≥ 10 mg/l) and inactive disease (in remission, CRP level \u003c 10 mg/l) [26] and in healthy controls. There were no statistically significant differences in IFN-γ production without IL-10 among these three groups (Fig. 2a), but the inhibitory effect of IL-10 on IFN-γ production was significantly limited in the active RA group as compared with the inactive RA group and healthy controls (percentage decrease: active RA, 2.9 ± 14.4%; inactive RA, 45.6 ± 14.4%; controls, 65.8 ± 7.9%) (Fig. 2b). As a consequence, CD4+ T cells from active RA patients produced higher levels of IFN-γ in the presence of 1 ng/ml IL-10 than did normal CD4+ T cells (Fig. 2a).\nIn addition, we compared IL-2 production by CD4+ T cells after CD3 and CD28 costimulation in the presence of IL-10 in active RA patients and in healthy controls. Similarly, IL-2 production was not affected by 1 ng/ml IL-10 in RA patients (percentage decrease, -2.1 ± 13.8%), while it was significantly reduced in healthy controls (61.1 ± 13.7%; P \u003c 0.05). Taken together, these results indicate that RA CD4+ T cells become less susceptible to the immunoregulatory effect of IL-10 during the active phase."}
bionlp-st-ge-2016-uniprot
{"project":"bionlp-st-ge-2016-uniprot","denotations":[{"id":"T13115","span":{"begin":1998,"end":2002},"obj":"http://www.uniprot.org/uniprot/P60568"},{"id":"T13114","span":{"begin":1850,"end":1854},"obj":"http://www.uniprot.org/uniprot/P60568"},{"id":"T13113","span":{"begin":1888,"end":1891},"obj":"http://www.uniprot.org/uniprot/P09693"},{"id":"T13112","span":{"begin":1038,"end":1041},"obj":"http://www.uniprot.org/uniprot/P09693"},{"id":"T13111","span":{"begin":500,"end":503},"obj":"http://www.uniprot.org/uniprot/P09693"},{"id":"T13110","span":{"begin":1888,"end":1891},"obj":"http://www.uniprot.org/uniprot/P07766"},{"id":"T13109","span":{"begin":1038,"end":1041},"obj":"http://www.uniprot.org/uniprot/P07766"},{"id":"T13108","span":{"begin":500,"end":503},"obj":"http://www.uniprot.org/uniprot/P07766"},{"id":"T13107","span":{"begin":1888,"end":1891},"obj":"http://www.uniprot.org/uniprot/P04234"},{"id":"T13106","span":{"begin":1038,"end":1041},"obj":"http://www.uniprot.org/uniprot/P04234"},{"id":"T13105","span":{"begin":500,"end":503},"obj":"http://www.uniprot.org/uniprot/P04234"},{"id":"T13104","span":{"begin":1888,"end":1891},"obj":"http://www.uniprot.org/uniprot/P20963"},{"id":"T13103","span":{"begin":1038,"end":1041},"obj":"http://www.uniprot.org/uniprot/P20963"},{"id":"T13102","span":{"begin":500,"end":503},"obj":"http://www.uniprot.org/uniprot/P20963"},{"id":"T13101","span":{"begin":1896,"end":1900},"obj":"http://www.uniprot.org/uniprot/P10747"},{"id":"T13100","span":{"begin":1046,"end":1050},"obj":"http://www.uniprot.org/uniprot/P10747"},{"id":"T13099","span":{"begin":522,"end":526},"obj":"http://www.uniprot.org/uniprot/P10747"},{"id":"T13098","span":{"begin":231,"end":235},"obj":"http://www.uniprot.org/uniprot/P10747"},{"id":"T13097","span":{"begin":74,"end":78},"obj":"http://www.uniprot.org/uniprot/P10747"},{"id":"T13096","span":{"begin":2228,"end":2231},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T13095","span":{"begin":1869,"end":1872},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T13094","span":{"begin":1801,"end":1804},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T13093","span":{"begin":1683,"end":1686},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T13092","span":{"begin":1019,"end":1022},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T13091","span":{"begin":788,"end":791},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T13090","span":{"begin":699,"end":702},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T13089","span":{"begin":384,"end":387},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T13088","span":{"begin":349,"end":352},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T13087","span":{"begin":57,"end":60},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T13086","span":{"begin":1746,"end":1751},"obj":"http://www.uniprot.org/uniprot/P01579"},{"id":"T13085","span":{"begin":1432,"end":1437},"obj":"http://www.uniprot.org/uniprot/P01579"},{"id":"T13073","span":{"begin":1352,"end":1357},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T13072","span":{"begin":1092,"end":1097},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T13071","span":{"begin":932,"end":937},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T13070","span":{"begin":878,"end":883},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T13069","span":{"begin":769,"end":774},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T13068","span":{"begin":578,"end":583},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T13067","span":{"begin":365,"end":370},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T13066","span":{"begin":175,"end":180},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T13065","span":{"begin":14,"end":19},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T13084","span":{"begin":1327,"end":1332},"obj":"http://www.uniprot.org/uniprot/P01579"},{"id":"T13083","span":{"begin":999,"end":1004},"obj":"http://www.uniprot.org/uniprot/P01579"},{"id":"T13082","span":{"begin":845,"end":850},"obj":"http://www.uniprot.org/uniprot/P01579"},{"id":"T13081","span":{"begin":662,"end":667},"obj":"http://www.uniprot.org/uniprot/P01579"},{"id":"T13080","span":{"begin":602,"end":607},"obj":"http://www.uniprot.org/uniprot/P01579"},{"id":"T13079","span":{"begin":34,"end":39},"obj":"http://www.uniprot.org/uniprot/P01579"},{"id":"T13078","span":{"begin":2299,"end":2304},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T13077","span":{"begin":2042,"end":2047},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T13076","span":{"begin":1934,"end":1939},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T13075","span":{"begin":1779,"end":1784},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T13074","span":{"begin":1423,"end":1428},"obj":"http://www.uniprot.org/uniprot/P22301"}],"namespaces":[{"prefix":"_base","uri":"http://www.uniprot.org/uniprot/"}],"text":"Resistance to IL-10 inhibition of IFN-γ production in RA CD4+ T cells\nThe CD28 costimulatory pathway is crucial for effective antigen-specific T-cell cytokine production, and IL-10 can directly suppress this response by inhibiting CD28 tyrosine phosphorylation and binding of phosphatidylinositol 3-kinase [24]. To evaluate the responsiveness of RA CD4+ T cells to IL-10, purified PB CD4+ T cells from three patients with active RA and from three healthy controls were stimulated by immobilized anti-CD3 antibody and anti-CD28 antibody with or without diluted concentrations of IL-10 for 36 hours, and IFN-γ production was measured by ELISA. As shown in Fig. 1, IFN-γ production by activated normal CD4+ T cells was mostly inhibited at concentrations as low as 1 ng/ml IL-10. However, RA CD4+ T cells were able to produce significant amounts of IFN-γ in the presence of 1 ng/ml IL-10, and the maximal but not complete inhibition by IL-10 was obtained at 10–100 ng/ml.\nWe thus compared the levels of IFN-γ production by CD4+ T cells after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 in RA patients with active disease (multiple inflammatory joints, CRP level ≥ 10 mg/l) and inactive disease (in remission, CRP level \u003c 10 mg/l) [26] and in healthy controls. There were no statistically significant differences in IFN-γ production without IL-10 among these three groups (Fig. 2a), but the inhibitory effect of IL-10 on IFN-γ production was significantly limited in the active RA group as compared with the inactive RA group and healthy controls (percentage decrease: active RA, 2.9 ± 14.4%; inactive RA, 45.6 ± 14.4%; controls, 65.8 ± 7.9%) (Fig. 2b). As a consequence, CD4+ T cells from active RA patients produced higher levels of IFN-γ in the presence of 1 ng/ml IL-10 than did normal CD4+ T cells (Fig. 2a).\nIn addition, we compared IL-2 production by CD4+ T cells after CD3 and CD28 costimulation in the presence of IL-10 in active RA patients and in healthy controls. Similarly, IL-2 production was not affected by 1 ng/ml IL-10 in RA patients (percentage decrease, -2.1 ± 13.8%), while it was significantly reduced in healthy controls (61.1 ± 13.7%; P \u003c 0.05). Taken together, these results indicate that RA CD4+ T cells become less susceptible to the immunoregulatory effect of IL-10 during the active phase."}
GO-BP
{"project":"GO-BP","denotations":[{"id":"T12824","span":{"begin":1998,"end":2013},"obj":"http://purl.obolibrary.org/obo/GO_0032663"},{"id":"T12823","span":{"begin":1850,"end":1865},"obj":"http://purl.obolibrary.org/obo/GO_0032663"},{"id":"T12822","span":{"begin":1998,"end":2013},"obj":"http://purl.obolibrary.org/obo/GO_0032623"},{"id":"T12821","span":{"begin":1850,"end":1865},"obj":"http://purl.obolibrary.org/obo/GO_0032623"},{"id":"T12820","span":{"begin":666,"end":691},"obj":"http://purl.obolibrary.org/obo/GO_0032729"},{"id":"T12819","span":{"begin":245,"end":260},"obj":"http://purl.obolibrary.org/obo/GO_0016310"},{"id":"T12818","span":{"begin":159,"end":180},"obj":"http://purl.obolibrary.org/obo/GO_0032613"},{"id":"T12817","span":{"begin":159,"end":180},"obj":"http://purl.obolibrary.org/obo/GO_0032653"},{"id":"T12816","span":{"begin":150,"end":169},"obj":"http://purl.obolibrary.org/obo/GO_0001816"},{"id":"T12815","span":{"begin":145,"end":169},"obj":"http://purl.obolibrary.org/obo/GO_0035745"},{"id":"T12814","span":{"begin":145,"end":169},"obj":"http://purl.obolibrary.org/obo/GO_0035744"},{"id":"T12813","span":{"begin":145,"end":169},"obj":"http://purl.obolibrary.org/obo/GO_0002368"},{"id":"T12812","span":{"begin":145,"end":169},"obj":"http://purl.obolibrary.org/obo/GO_0032762"},{"id":"T12811","span":{"begin":145,"end":169},"obj":"http://purl.obolibrary.org/obo/GO_0002371"},{"id":"T12810","span":{"begin":145,"end":169},"obj":"http://purl.obolibrary.org/obo/GO_0002370"},{"id":"T12809","span":{"begin":143,"end":169},"obj":"http://purl.obolibrary.org/obo/GO_0002724"},{"id":"T12808","span":{"begin":143,"end":169},"obj":"http://purl.obolibrary.org/obo/GO_0002369"},{"id":"T12807","span":{"begin":20,"end":39},"obj":"http://purl.obolibrary.org/obo/GO_1902714"}],"text":"Resistance to IL-10 inhibition of IFN-γ production in RA CD4+ T cells\nThe CD28 costimulatory pathway is crucial for effective antigen-specific T-cell cytokine production, and IL-10 can directly suppress this response by inhibiting CD28 tyrosine phosphorylation and binding of phosphatidylinositol 3-kinase [24]. To evaluate the responsiveness of RA CD4+ T cells to IL-10, purified PB CD4+ T cells from three patients with active RA and from three healthy controls were stimulated by immobilized anti-CD3 antibody and anti-CD28 antibody with or without diluted concentrations of IL-10 for 36 hours, and IFN-γ production was measured by ELISA. As shown in Fig. 1, IFN-γ production by activated normal CD4+ T cells was mostly inhibited at concentrations as low as 1 ng/ml IL-10. However, RA CD4+ T cells were able to produce significant amounts of IFN-γ in the presence of 1 ng/ml IL-10, and the maximal but not complete inhibition by IL-10 was obtained at 10–100 ng/ml.\nWe thus compared the levels of IFN-γ production by CD4+ T cells after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 in RA patients with active disease (multiple inflammatory joints, CRP level ≥ 10 mg/l) and inactive disease (in remission, CRP level \u003c 10 mg/l) [26] and in healthy controls. There were no statistically significant differences in IFN-γ production without IL-10 among these three groups (Fig. 2a), but the inhibitory effect of IL-10 on IFN-γ production was significantly limited in the active RA group as compared with the inactive RA group and healthy controls (percentage decrease: active RA, 2.9 ± 14.4%; inactive RA, 45.6 ± 14.4%; controls, 65.8 ± 7.9%) (Fig. 2b). As a consequence, CD4+ T cells from active RA patients produced higher levels of IFN-γ in the presence of 1 ng/ml IL-10 than did normal CD4+ T cells (Fig. 2a).\nIn addition, we compared IL-2 production by CD4+ T cells after CD3 and CD28 costimulation in the presence of IL-10 in active RA patients and in healthy controls. Similarly, IL-2 production was not affected by 1 ng/ml IL-10 in RA patients (percentage decrease, -2.1 ± 13.8%), while it was significantly reduced in healthy controls (61.1 ± 13.7%; P \u003c 0.05). Taken together, these results indicate that RA CD4+ T cells become less susceptible to the immunoregulatory effect of IL-10 during the active phase."}
GO-CC
{"project":"GO-CC","denotations":[{"id":"T12964","span":{"begin":527,"end":535},"obj":"http://purl.obolibrary.org/obo/GO_0042571"},{"id":"T12963","span":{"begin":504,"end":512},"obj":"http://purl.obolibrary.org/obo/GO_0042571"},{"id":"T12962","span":{"begin":527,"end":535},"obj":"http://purl.obolibrary.org/obo/GO_0019815"},{"id":"T12961","span":{"begin":504,"end":512},"obj":"http://purl.obolibrary.org/obo/GO_0019815"},{"id":"T12960","span":{"begin":2235,"end":2240},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T12959","span":{"begin":1876,"end":1881},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T12958","span":{"begin":1808,"end":1813},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T12957","span":{"begin":1690,"end":1695},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T12956","span":{"begin":1026,"end":1031},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T12955","span":{"begin":795,"end":800},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T12954","span":{"begin":706,"end":711},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T12953","span":{"begin":391,"end":396},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T12952","span":{"begin":356,"end":361},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T12951","span":{"begin":64,"end":69},"obj":"http://purl.obolibrary.org/obo/GO_0005623"}],"text":"Resistance to IL-10 inhibition of IFN-γ production in RA CD4+ T cells\nThe CD28 costimulatory pathway is crucial for effective antigen-specific T-cell cytokine production, and IL-10 can directly suppress this response by inhibiting CD28 tyrosine phosphorylation and binding of phosphatidylinositol 3-kinase [24]. To evaluate the responsiveness of RA CD4+ T cells to IL-10, purified PB CD4+ T cells from three patients with active RA and from three healthy controls were stimulated by immobilized anti-CD3 antibody and anti-CD28 antibody with or without diluted concentrations of IL-10 for 36 hours, and IFN-γ production was measured by ELISA. As shown in Fig. 1, IFN-γ production by activated normal CD4+ T cells was mostly inhibited at concentrations as low as 1 ng/ml IL-10. However, RA CD4+ T cells were able to produce significant amounts of IFN-γ in the presence of 1 ng/ml IL-10, and the maximal but not complete inhibition by IL-10 was obtained at 10–100 ng/ml.\nWe thus compared the levels of IFN-γ production by CD4+ T cells after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 in RA patients with active disease (multiple inflammatory joints, CRP level ≥ 10 mg/l) and inactive disease (in remission, CRP level \u003c 10 mg/l) [26] and in healthy controls. There were no statistically significant differences in IFN-γ production without IL-10 among these three groups (Fig. 2a), but the inhibitory effect of IL-10 on IFN-γ production was significantly limited in the active RA group as compared with the inactive RA group and healthy controls (percentage decrease: active RA, 2.9 ± 14.4%; inactive RA, 45.6 ± 14.4%; controls, 65.8 ± 7.9%) (Fig. 2b). As a consequence, CD4+ T cells from active RA patients produced higher levels of IFN-γ in the presence of 1 ng/ml IL-10 than did normal CD4+ T cells (Fig. 2a).\nIn addition, we compared IL-2 production by CD4+ T cells after CD3 and CD28 costimulation in the presence of IL-10 in active RA patients and in healthy controls. Similarly, IL-2 production was not affected by 1 ng/ml IL-10 in RA patients (percentage decrease, -2.1 ± 13.8%), while it was significantly reduced in healthy controls (61.1 ± 13.7%; P \u003c 0.05). Taken together, these results indicate that RA CD4+ T cells become less susceptible to the immunoregulatory effect of IL-10 during the active phase."}
GO-MF
{"project":"GO-MF","denotations":[{"id":"T12950","span":{"begin":1998,"end":2002},"obj":"http://purl.obolibrary.org/obo/GO_0005134"},{"id":"T12949","span":{"begin":1850,"end":1854},"obj":"http://purl.obolibrary.org/obo/GO_0005134"},{"id":"T12948","span":{"begin":527,"end":535},"obj":"http://purl.obolibrary.org/obo/GO_0003823"},{"id":"T12947","span":{"begin":504,"end":512},"obj":"http://purl.obolibrary.org/obo/GO_0003823"},{"id":"T12946","span":{"begin":265,"end":305},"obj":"http://purl.obolibrary.org/obo/GO_0043548"},{"id":"T12945","span":{"begin":265,"end":298},"obj":"http://purl.obolibrary.org/obo/GO_0032266"},{"id":"T12944","span":{"begin":265,"end":272},"obj":"http://purl.obolibrary.org/obo/GO_0005488"},{"id":"T12943","span":{"begin":2299,"end":2304},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T12942","span":{"begin":2042,"end":2047},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T12941","span":{"begin":1934,"end":1939},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T12940","span":{"begin":1779,"end":1784},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T12939","span":{"begin":1423,"end":1428},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T12938","span":{"begin":1352,"end":1357},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T12937","span":{"begin":1092,"end":1097},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T12936","span":{"begin":932,"end":937},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T12935","span":{"begin":878,"end":883},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T12934","span":{"begin":769,"end":774},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T12933","span":{"begin":578,"end":583},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T12932","span":{"begin":365,"end":370},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T12931","span":{"begin":175,"end":180},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T12930","span":{"begin":14,"end":19},"obj":"http://purl.obolibrary.org/obo/GO_0005141"}],"text":"Resistance to IL-10 inhibition of IFN-γ production in RA CD4+ T cells\nThe CD28 costimulatory pathway is crucial for effective antigen-specific T-cell cytokine production, and IL-10 can directly suppress this response by inhibiting CD28 tyrosine phosphorylation and binding of phosphatidylinositol 3-kinase [24]. To evaluate the responsiveness of RA CD4+ T cells to IL-10, purified PB CD4+ T cells from three patients with active RA and from three healthy controls were stimulated by immobilized anti-CD3 antibody and anti-CD28 antibody with or without diluted concentrations of IL-10 for 36 hours, and IFN-γ production was measured by ELISA. As shown in Fig. 1, IFN-γ production by activated normal CD4+ T cells was mostly inhibited at concentrations as low as 1 ng/ml IL-10. However, RA CD4+ T cells were able to produce significant amounts of IFN-γ in the presence of 1 ng/ml IL-10, and the maximal but not complete inhibition by IL-10 was obtained at 10–100 ng/ml.\nWe thus compared the levels of IFN-γ production by CD4+ T cells after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 in RA patients with active disease (multiple inflammatory joints, CRP level ≥ 10 mg/l) and inactive disease (in remission, CRP level \u003c 10 mg/l) [26] and in healthy controls. There were no statistically significant differences in IFN-γ production without IL-10 among these three groups (Fig. 2a), but the inhibitory effect of IL-10 on IFN-γ production was significantly limited in the active RA group as compared with the inactive RA group and healthy controls (percentage decrease: active RA, 2.9 ± 14.4%; inactive RA, 45.6 ± 14.4%; controls, 65.8 ± 7.9%) (Fig. 2b). As a consequence, CD4+ T cells from active RA patients produced higher levels of IFN-γ in the presence of 1 ng/ml IL-10 than did normal CD4+ T cells (Fig. 2a).\nIn addition, we compared IL-2 production by CD4+ T cells after CD3 and CD28 costimulation in the presence of IL-10 in active RA patients and in healthy controls. Similarly, IL-2 production was not affected by 1 ng/ml IL-10 in RA patients (percentage decrease, -2.1 ± 13.8%), while it was significantly reduced in healthy controls (61.1 ± 13.7%; P \u003c 0.05). Taken together, these results indicate that RA CD4+ T cells become less susceptible to the immunoregulatory effect of IL-10 during the active phase."}
sentences
{"project":"sentences","denotations":[{"id":"T12806","span":{"begin":2181,"end":2329},"obj":"Sentence"},{"id":"T12805","span":{"begin":1987,"end":2180},"obj":"Sentence"},{"id":"T12804","span":{"begin":1825,"end":1986},"obj":"Sentence"},{"id":"T12803","span":{"begin":1665,"end":1824},"obj":"Sentence"},{"id":"T12802","span":{"begin":1272,"end":1664},"obj":"Sentence"},{"id":"T12801","span":{"begin":968,"end":1271},"obj":"Sentence"},{"id":"T12800","span":{"begin":776,"end":967},"obj":"Sentence"},{"id":"T12799","span":{"begin":642,"end":775},"obj":"Sentence"},{"id":"T12798","span":{"begin":312,"end":641},"obj":"Sentence"},{"id":"T12797","span":{"begin":70,"end":311},"obj":"Sentence"},{"id":"T12796","span":{"begin":0,"end":69},"obj":"Sentence"},{"id":"T92","span":{"begin":0,"end":69},"obj":"Sentence"},{"id":"T93","span":{"begin":70,"end":311},"obj":"Sentence"},{"id":"T94","span":{"begin":312,"end":641},"obj":"Sentence"},{"id":"T95","span":{"begin":642,"end":775},"obj":"Sentence"},{"id":"T96","span":{"begin":776,"end":967},"obj":"Sentence"},{"id":"T97","span":{"begin":968,"end":1271},"obj":"Sentence"},{"id":"T98","span":{"begin":1272,"end":1664},"obj":"Sentence"},{"id":"T99","span":{"begin":1665,"end":1824},"obj":"Sentence"},{"id":"T100","span":{"begin":1825,"end":1986},"obj":"Sentence"},{"id":"T101","span":{"begin":1987,"end":2180},"obj":"Sentence"},{"id":"T102","span":{"begin":2181,"end":2329},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Resistance to IL-10 inhibition of IFN-γ production in RA CD4+ T cells\nThe CD28 costimulatory pathway is crucial for effective antigen-specific T-cell cytokine production, and IL-10 can directly suppress this response by inhibiting CD28 tyrosine phosphorylation and binding of phosphatidylinositol 3-kinase [24]. To evaluate the responsiveness of RA CD4+ T cells to IL-10, purified PB CD4+ T cells from three patients with active RA and from three healthy controls were stimulated by immobilized anti-CD3 antibody and anti-CD28 antibody with or without diluted concentrations of IL-10 for 36 hours, and IFN-γ production was measured by ELISA. As shown in Fig. 1, IFN-γ production by activated normal CD4+ T cells was mostly inhibited at concentrations as low as 1 ng/ml IL-10. However, RA CD4+ T cells were able to produce significant amounts of IFN-γ in the presence of 1 ng/ml IL-10, and the maximal but not complete inhibition by IL-10 was obtained at 10–100 ng/ml.\nWe thus compared the levels of IFN-γ production by CD4+ T cells after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 in RA patients with active disease (multiple inflammatory joints, CRP level ≥ 10 mg/l) and inactive disease (in remission, CRP level \u003c 10 mg/l) [26] and in healthy controls. There were no statistically significant differences in IFN-γ production without IL-10 among these three groups (Fig. 2a), but the inhibitory effect of IL-10 on IFN-γ production was significantly limited in the active RA group as compared with the inactive RA group and healthy controls (percentage decrease: active RA, 2.9 ± 14.4%; inactive RA, 45.6 ± 14.4%; controls, 65.8 ± 7.9%) (Fig. 2b). As a consequence, CD4+ T cells from active RA patients produced higher levels of IFN-γ in the presence of 1 ng/ml IL-10 than did normal CD4+ T cells (Fig. 2a).\nIn addition, we compared IL-2 production by CD4+ T cells after CD3 and CD28 costimulation in the presence of IL-10 in active RA patients and in healthy controls. Similarly, IL-2 production was not affected by 1 ng/ml IL-10 in RA patients (percentage decrease, -2.1 ± 13.8%), while it was significantly reduced in healthy controls (61.1 ± 13.7%; P \u003c 0.05). Taken together, these results indicate that RA CD4+ T cells become less susceptible to the immunoregulatory effect of IL-10 during the active phase."}
simple1
{"project":"simple1","denotations":[{"id":"T13138","span":{"begin":1038,"end":1041},"obj":"Protein"},{"id":"T13137","span":{"begin":1019,"end":1022},"obj":"Protein"},{"id":"T13136","span":{"begin":999,"end":1004},"obj":"Protein"},{"id":"T13135","span":{"begin":932,"end":937},"obj":"Protein"},{"id":"T13134","span":{"begin":878,"end":883},"obj":"Protein"},{"id":"T13133","span":{"begin":845,"end":850},"obj":"Protein"},{"id":"T13132","span":{"begin":788,"end":791},"obj":"Protein"},{"id":"T13131","span":{"begin":769,"end":774},"obj":"Protein"},{"id":"T13130","span":{"begin":699,"end":702},"obj":"Protein"},{"id":"T13129","span":{"begin":662,"end":667},"obj":"Protein"},{"id":"T13128","span":{"begin":602,"end":607},"obj":"Protein"},{"id":"T13127","span":{"begin":578,"end":583},"obj":"Protein"},{"id":"T13126","span":{"begin":522,"end":526},"obj":"Protein"},{"id":"T13125","span":{"begin":500,"end":503},"obj":"Protein"},{"id":"T13124","span":{"begin":384,"end":387},"obj":"Protein"},{"id":"T13123","span":{"begin":365,"end":370},"obj":"Protein"},{"id":"T13122","span":{"begin":349,"end":352},"obj":"Protein"},{"id":"T13121","span":{"begin":231,"end":235},"obj":"Protein"},{"id":"T13120","span":{"begin":175,"end":180},"obj":"Protein"},{"id":"T13119","span":{"begin":74,"end":78},"obj":"Protein"},{"id":"T13118","span":{"begin":57,"end":60},"obj":"Protein"},{"id":"T13117","span":{"begin":34,"end":39},"obj":"Protein"},{"id":"T13116","span":{"begin":14,"end":19},"obj":"Protein"},{"id":"T13156","span":{"begin":2299,"end":2304},"obj":"Protein"},{"id":"T13155","span":{"begin":2228,"end":2231},"obj":"Protein"},{"id":"T13154","span":{"begin":2042,"end":2047},"obj":"Protein"},{"id":"T13153","span":{"begin":1998,"end":2002},"obj":"Protein"},{"id":"T13152","span":{"begin":1934,"end":1939},"obj":"Protein"},{"id":"T13151","span":{"begin":1896,"end":1900},"obj":"Protein"},{"id":"T13150","span":{"begin":1869,"end":1872},"obj":"Protein"},{"id":"T13149","span":{"begin":1850,"end":1854},"obj":"Protein"},{"id":"T13148","span":{"begin":1801,"end":1804},"obj":"Protein"},{"id":"T13147","span":{"begin":1779,"end":1784},"obj":"Protein"},{"id":"T13146","span":{"begin":1746,"end":1751},"obj":"Protein"},{"id":"T13145","span":{"begin":1683,"end":1686},"obj":"Protein"},{"id":"T13144","span":{"begin":1432,"end":1437},"obj":"Protein"},{"id":"T13143","span":{"begin":1423,"end":1428},"obj":"Protein"},{"id":"T13142","span":{"begin":1352,"end":1357},"obj":"Protein"},{"id":"T13141","span":{"begin":1327,"end":1332},"obj":"Protein"},{"id":"T13140","span":{"begin":1092,"end":1097},"obj":"Protein"},{"id":"T13139","span":{"begin":1046,"end":1050},"obj":"Protein"}],"text":"Resistance to IL-10 inhibition of IFN-γ production in RA CD4+ T cells\nThe CD28 costimulatory pathway is crucial for effective antigen-specific T-cell cytokine production, and IL-10 can directly suppress this response by inhibiting CD28 tyrosine phosphorylation and binding of phosphatidylinositol 3-kinase [24]. To evaluate the responsiveness of RA CD4+ T cells to IL-10, purified PB CD4+ T cells from three patients with active RA and from three healthy controls were stimulated by immobilized anti-CD3 antibody and anti-CD28 antibody with or without diluted concentrations of IL-10 for 36 hours, and IFN-γ production was measured by ELISA. As shown in Fig. 1, IFN-γ production by activated normal CD4+ T cells was mostly inhibited at concentrations as low as 1 ng/ml IL-10. However, RA CD4+ T cells were able to produce significant amounts of IFN-γ in the presence of 1 ng/ml IL-10, and the maximal but not complete inhibition by IL-10 was obtained at 10–100 ng/ml.\nWe thus compared the levels of IFN-γ production by CD4+ T cells after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 in RA patients with active disease (multiple inflammatory joints, CRP level ≥ 10 mg/l) and inactive disease (in remission, CRP level \u003c 10 mg/l) [26] and in healthy controls. There were no statistically significant differences in IFN-γ production without IL-10 among these three groups (Fig. 2a), but the inhibitory effect of IL-10 on IFN-γ production was significantly limited in the active RA group as compared with the inactive RA group and healthy controls (percentage decrease: active RA, 2.9 ± 14.4%; inactive RA, 45.6 ± 14.4%; controls, 65.8 ± 7.9%) (Fig. 2b). As a consequence, CD4+ T cells from active RA patients produced higher levels of IFN-γ in the presence of 1 ng/ml IL-10 than did normal CD4+ T cells (Fig. 2a).\nIn addition, we compared IL-2 production by CD4+ T cells after CD3 and CD28 costimulation in the presence of IL-10 in active RA patients and in healthy controls. Similarly, IL-2 production was not affected by 1 ng/ml IL-10 in RA patients (percentage decrease, -2.1 ± 13.8%), while it was significantly reduced in healthy controls (61.1 ± 13.7%; P \u003c 0.05). Taken together, these results indicate that RA CD4+ T cells become less susceptible to the immunoregulatory effect of IL-10 during the active phase."}
BioNLP16_DUT
{"project":"BioNLP16_DUT","denotations":[{"id":"T14405","span":{"begin":2003,"end":2013},"obj":"Gene_expression"},{"id":"T14404","span":{"begin":2022,"end":2030},"obj":"Regulation"},{"id":"T14403","span":{"begin":1855,"end":1865},"obj":"Gene_expression"},{"id":"T14402","span":{"begin":1438,"end":1448},"obj":"Gene_expression"},{"id":"T14401","span":{"begin":1333,"end":1343},"obj":"Gene_expression"},{"id":"T14400","span":{"begin":1005,"end":1015},"obj":"Gene_expression"},{"id":"T14399","span":{"begin":814,"end":821},"obj":"Gene_expression"},{"id":"T14398","span":{"begin":723,"end":732},"obj":"Negative_regulation"},{"id":"T14397","span":{"begin":668,"end":678},"obj":"Gene_expression"},{"id":"T14396","span":{"begin":608,"end":618},"obj":"Gene_expression"},{"id":"T14395","span":{"begin":245,"end":260},"obj":"Phosphorylation"},{"id":"T14394","span":{"begin":220,"end":230},"obj":"Negative_regulation"},{"id":"T14393","span":{"begin":20,"end":30},"obj":"Negative_regulation"},{"id":"T14392","span":{"begin":40,"end":50},"obj":"Gene_expression"},{"id":"T14391","span":{"begin":2299,"end":2304},"obj":"Protein"},{"id":"T14390","span":{"begin":2228,"end":2231},"obj":"Protein"},{"id":"T14389","span":{"begin":2042,"end":2047},"obj":"Protein"},{"id":"T14388","span":{"begin":1998,"end":2002},"obj":"Protein"},{"id":"T14387","span":{"begin":1934,"end":1939},"obj":"Protein"},{"id":"T14386","span":{"begin":1896,"end":1900},"obj":"Protein"},{"id":"T14385","span":{"begin":1869,"end":1872},"obj":"Protein"},{"id":"T14384","span":{"begin":1850,"end":1854},"obj":"Protein"},{"id":"T14383","span":{"begin":1801,"end":1804},"obj":"Protein"},{"id":"T14382","span":{"begin":1779,"end":1784},"obj":"Protein"},{"id":"T14381","span":{"begin":1746,"end":1751},"obj":"Protein"},{"id":"T14380","span":{"begin":1683,"end":1686},"obj":"Protein"},{"id":"T14379","span":{"begin":1432,"end":1437},"obj":"Protein"},{"id":"T14378","span":{"begin":1423,"end":1428},"obj":"Protein"},{"id":"T14377","span":{"begin":1352,"end":1357},"obj":"Protein"},{"id":"T14376","span":{"begin":1327,"end":1332},"obj":"Protein"},{"id":"T14375","span":{"begin":1092,"end":1097},"obj":"Protein"},{"id":"T14351","span":{"begin":14,"end":19},"obj":"Protein"},{"id":"T14374","span":{"begin":1046,"end":1050},"obj":"Protein"},{"id":"T14373","span":{"begin":1038,"end":1041},"obj":"Protein"},{"id":"T14372","span":{"begin":1019,"end":1022},"obj":"Protein"},{"id":"T14371","span":{"begin":999,"end":1004},"obj":"Protein"},{"id":"T14370","span":{"begin":932,"end":937},"obj":"Protein"},{"id":"T14369","span":{"begin":878,"end":883},"obj":"Protein"},{"id":"T14368","span":{"begin":845,"end":850},"obj":"Protein"},{"id":"T14367","span":{"begin":788,"end":791},"obj":"Protein"},{"id":"T14366","span":{"begin":769,"end":774},"obj":"Protein"},{"id":"T14365","span":{"begin":699,"end":702},"obj":"Protein"},{"id":"T14364","span":{"begin":662,"end":667},"obj":"Protein"},{"id":"T14363","span":{"begin":384,"end":387},"obj":"Protein"},{"id":"T14362","span":{"begin":365,"end":370},"obj":"Protein"},{"id":"T14361","span":{"begin":349,"end":352},"obj":"Protein"},{"id":"T14360","span":{"begin":602,"end":607},"obj":"Protein"},{"id":"T14359","span":{"begin":578,"end":583},"obj":"Protein"},{"id":"T14358","span":{"begin":522,"end":526},"obj":"Protein"},{"id":"T14357","span":{"begin":500,"end":503},"obj":"Protein"},{"id":"T14356","span":{"begin":231,"end":235},"obj":"Protein"},{"id":"T14355","span":{"begin":175,"end":180},"obj":"Protein"},{"id":"T14354","span":{"begin":74,"end":78},"obj":"Protein"},{"id":"T14353","span":{"begin":57,"end":60},"obj":"Protein"},{"id":"T14352","span":{"begin":34,"end":39},"obj":"Protein"}],"relations":[{"id":"R7409","pred":"themeOf","subj":"T14352","obj":"T14392"},{"id":"R7410","pred":"causeOf","subj":"T14355","obj":"T14394"},{"id":"R7411","pred":"themeOf","subj":"T14356","obj":"T14395"},{"id":"R7412","pred":"themeOf","subj":"T14360","obj":"T14396"},{"id":"R7413","pred":"themeOf","subj":"T14364","obj":"T14397"},{"id":"R7414","pred":"themeOf","subj":"T14368","obj":"T14399"},{"id":"R7415","pred":"themeOf","subj":"T14371","obj":"T14400"},{"id":"R7416","pred":"themeOf","subj":"T14376","obj":"T14401"},{"id":"R7417","pred":"themeOf","subj":"T14379","obj":"T14402"},{"id":"R7418","pred":"themeOf","subj":"T14384","obj":"T14403"},{"id":"R7419","pred":"themeOf","subj":"T14388","obj":"T14405"},{"id":"R7420","pred":"themeOf","subj":"T14392","obj":"T14393"},{"id":"R7421","pred":"themeOf","subj":"T14395","obj":"T14394"},{"id":"R7422","pred":"themeOf","subj":"T14397","obj":"T14398"},{"id":"R7423","pred":"themeOf","subj":"T14405","obj":"T14404"}],"text":"Resistance to IL-10 inhibition of IFN-γ production in RA CD4+ T cells\nThe CD28 costimulatory pathway is crucial for effective antigen-specific T-cell cytokine production, and IL-10 can directly suppress this response by inhibiting CD28 tyrosine phosphorylation and binding of phosphatidylinositol 3-kinase [24]. To evaluate the responsiveness of RA CD4+ T cells to IL-10, purified PB CD4+ T cells from three patients with active RA and from three healthy controls were stimulated by immobilized anti-CD3 antibody and anti-CD28 antibody with or without diluted concentrations of IL-10 for 36 hours, and IFN-γ production was measured by ELISA. As shown in Fig. 1, IFN-γ production by activated normal CD4+ T cells was mostly inhibited at concentrations as low as 1 ng/ml IL-10. However, RA CD4+ T cells were able to produce significant amounts of IFN-γ in the presence of 1 ng/ml IL-10, and the maximal but not complete inhibition by IL-10 was obtained at 10–100 ng/ml.\nWe thus compared the levels of IFN-γ production by CD4+ T cells after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 in RA patients with active disease (multiple inflammatory joints, CRP level ≥ 10 mg/l) and inactive disease (in remission, CRP level \u003c 10 mg/l) [26] and in healthy controls. There were no statistically significant differences in IFN-γ production without IL-10 among these three groups (Fig. 2a), but the inhibitory effect of IL-10 on IFN-γ production was significantly limited in the active RA group as compared with the inactive RA group and healthy controls (percentage decrease: active RA, 2.9 ± 14.4%; inactive RA, 45.6 ± 14.4%; controls, 65.8 ± 7.9%) (Fig. 2b). As a consequence, CD4+ T cells from active RA patients produced higher levels of IFN-γ in the presence of 1 ng/ml IL-10 than did normal CD4+ T cells (Fig. 2a).\nIn addition, we compared IL-2 production by CD4+ T cells after CD3 and CD28 costimulation in the presence of IL-10 in active RA patients and in healthy controls. Similarly, IL-2 production was not affected by 1 ng/ml IL-10 in RA patients (percentage decrease, -2.1 ± 13.8%), while it was significantly reduced in healthy controls (61.1 ± 13.7%; P \u003c 0.05). Taken together, these results indicate that RA CD4+ T cells become less susceptible to the immunoregulatory effect of IL-10 during the active phase."}
BioNLP16_Messiy
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to IL-10 inhibition of IFN-γ production in RA CD4+ T cells\nThe CD28 costimulatory pathway is crucial for effective antigen-specific T-cell cytokine production, and IL-10 can directly suppress this response by inhibiting CD28 tyrosine phosphorylation and binding of phosphatidylinositol 3-kinase [24]. To evaluate the responsiveness of RA CD4+ T cells to IL-10, purified PB CD4+ T cells from three patients with active RA and from three healthy controls were stimulated by immobilized anti-CD3 antibody and anti-CD28 antibody with or without diluted concentrations of IL-10 for 36 hours, and IFN-γ production was measured by ELISA. As shown in Fig. 1, IFN-γ production by activated normal CD4+ T cells was mostly inhibited at concentrations as low as 1 ng/ml IL-10. However, RA CD4+ T cells were able to produce significant amounts of IFN-γ in the presence of 1 ng/ml IL-10, and the maximal but not complete inhibition by IL-10 was obtained at 10–100 ng/ml.\nWe thus compared the levels of IFN-γ production by CD4+ T cells after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 in RA patients with active disease (multiple inflammatory joints, CRP level ≥ 10 mg/l) and inactive disease (in remission, CRP level \u003c 10 mg/l) [26] and in healthy controls. There were no statistically significant differences in IFN-γ production without IL-10 among these three groups (Fig. 2a), but the inhibitory effect of IL-10 on IFN-γ production was significantly limited in the active RA group as compared with the inactive RA group and healthy controls (percentage decrease: active RA, 2.9 ± 14.4%; inactive RA, 45.6 ± 14.4%; controls, 65.8 ± 7.9%) (Fig. 2b). As a consequence, CD4+ T cells from active RA patients produced higher levels of IFN-γ in the presence of 1 ng/ml IL-10 than did normal CD4+ T cells (Fig. 2a).\nIn addition, we compared IL-2 production by CD4+ T cells after CD3 and CD28 costimulation in the presence of IL-10 in active RA patients and in healthy controls. Similarly, IL-2 production was not affected by 1 ng/ml IL-10 in RA patients (percentage decrease, -2.1 ± 13.8%), while it was significantly reduced in healthy controls (61.1 ± 13.7%; P \u003c 0.05). Taken together, these results indicate that RA CD4+ T cells become less susceptible to the immunoregulatory effect of IL-10 during the active phase."}
DLUT931
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to IL-10 inhibition of IFN-γ production in RA CD4+ T cells\nThe CD28 costimulatory pathway is crucial for effective antigen-specific T-cell cytokine production, and IL-10 can directly suppress this response by inhibiting CD28 tyrosine phosphorylation and binding of phosphatidylinositol 3-kinase [24]. To evaluate the responsiveness of RA CD4+ T cells to IL-10, purified PB CD4+ T cells from three patients with active RA and from three healthy controls were stimulated by immobilized anti-CD3 antibody and anti-CD28 antibody with or without diluted concentrations of IL-10 for 36 hours, and IFN-γ production was measured by ELISA. As shown in Fig. 1, IFN-γ production by activated normal CD4+ T cells was mostly inhibited at concentrations as low as 1 ng/ml IL-10. However, RA CD4+ T cells were able to produce significant amounts of IFN-γ in the presence of 1 ng/ml IL-10, and the maximal but not complete inhibition by IL-10 was obtained at 10–100 ng/ml.\nWe thus compared the levels of IFN-γ production by CD4+ T cells after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 in RA patients with active disease (multiple inflammatory joints, CRP level ≥ 10 mg/l) and inactive disease (in remission, CRP level \u003c 10 mg/l) [26] and in healthy controls. There were no statistically significant differences in IFN-γ production without IL-10 among these three groups (Fig. 2a), but the inhibitory effect of IL-10 on IFN-γ production was significantly limited in the active RA group as compared with the inactive RA group and healthy controls (percentage decrease: active RA, 2.9 ± 14.4%; inactive RA, 45.6 ± 14.4%; controls, 65.8 ± 7.9%) (Fig. 2b). As a consequence, CD4+ T cells from active RA patients produced higher levels of IFN-γ in the presence of 1 ng/ml IL-10 than did normal CD4+ T cells (Fig. 2a).\nIn addition, we compared IL-2 production by CD4+ T cells after CD3 and CD28 costimulation in the presence of IL-10 in active RA patients and in healthy controls. Similarly, IL-2 production was not affected by 1 ng/ml IL-10 in RA patients (percentage decrease, -2.1 ± 13.8%), while it was significantly reduced in healthy controls (61.1 ± 13.7%; P \u003c 0.05). Taken together, these results indicate that RA CD4+ T cells become less susceptible to the immunoregulatory effect of IL-10 during the active phase."}
bionlp-st-ge-2016-test-ihmc
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to IL-10 inhibition of IFN-γ production in RA CD4+ T cells\nThe CD28 costimulatory pathway is crucial for effective antigen-specific T-cell cytokine production, and IL-10 can directly suppress this response by inhibiting CD28 tyrosine phosphorylation and binding of phosphatidylinositol 3-kinase [24]. To evaluate the responsiveness of RA CD4+ T cells to IL-10, purified PB CD4+ T cells from three patients with active RA and from three healthy controls were stimulated by immobilized anti-CD3 antibody and anti-CD28 antibody with or without diluted concentrations of IL-10 for 36 hours, and IFN-γ production was measured by ELISA. As shown in Fig. 1, IFN-γ production by activated normal CD4+ T cells was mostly inhibited at concentrations as low as 1 ng/ml IL-10. However, RA CD4+ T cells were able to produce significant amounts of IFN-γ in the presence of 1 ng/ml IL-10, and the maximal but not complete inhibition by IL-10 was obtained at 10–100 ng/ml.\nWe thus compared the levels of IFN-γ production by CD4+ T cells after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 in RA patients with active disease (multiple inflammatory joints, CRP level ≥ 10 mg/l) and inactive disease (in remission, CRP level \u003c 10 mg/l) [26] and in healthy controls. There were no statistically significant differences in IFN-γ production without IL-10 among these three groups (Fig. 2a), but the inhibitory effect of IL-10 on IFN-γ production was significantly limited in the active RA group as compared with the inactive RA group and healthy controls (percentage decrease: active RA, 2.9 ± 14.4%; inactive RA, 45.6 ± 14.4%; controls, 65.8 ± 7.9%) (Fig. 2b). As a consequence, CD4+ T cells from active RA patients produced higher levels of IFN-γ in the presence of 1 ng/ml IL-10 than did normal CD4+ T cells (Fig. 2a).\nIn addition, we compared IL-2 production by CD4+ T cells after CD3 and CD28 costimulation in the presence of IL-10 in active RA patients and in healthy controls. Similarly, IL-2 production was not affected by 1 ng/ml IL-10 in RA patients (percentage decrease, -2.1 ± 13.8%), while it was significantly reduced in healthy controls (61.1 ± 13.7%; P \u003c 0.05). Taken together, these results indicate that RA CD4+ T cells become less susceptible to the immunoregulatory effect of IL-10 during the active phase."}
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to IL-10 inhibition of IFN-γ production in RA CD4+ T cells\nThe CD28 costimulatory pathway is crucial for effective antigen-specific T-cell cytokine production, and IL-10 can directly suppress this response by inhibiting CD28 tyrosine phosphorylation and binding of phosphatidylinositol 3-kinase [24]. To evaluate the responsiveness of RA CD4+ T cells to IL-10, purified PB CD4+ T cells from three patients with active RA and from three healthy controls were stimulated by immobilized anti-CD3 antibody and anti-CD28 antibody with or without diluted concentrations of IL-10 for 36 hours, and IFN-γ production was measured by ELISA. As shown in Fig. 1, IFN-γ production by activated normal CD4+ T cells was mostly inhibited at concentrations as low as 1 ng/ml IL-10. However, RA CD4+ T cells were able to produce significant amounts of IFN-γ in the presence of 1 ng/ml IL-10, and the maximal but not complete inhibition by IL-10 was obtained at 10–100 ng/ml.\nWe thus compared the levels of IFN-γ production by CD4+ T cells after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 in RA patients with active disease (multiple inflammatory joints, CRP level ≥ 10 mg/l) and inactive disease (in remission, CRP level \u003c 10 mg/l) [26] and in healthy controls. There were no statistically significant differences in IFN-γ production without IL-10 among these three groups (Fig. 2a), but the inhibitory effect of IL-10 on IFN-γ production was significantly limited in the active RA group as compared with the inactive RA group and healthy controls (percentage decrease: active RA, 2.9 ± 14.4%; inactive RA, 45.6 ± 14.4%; controls, 65.8 ± 7.9%) (Fig. 2b). As a consequence, CD4+ T cells from active RA patients produced higher levels of IFN-γ in the presence of 1 ng/ml IL-10 than did normal CD4+ T cells (Fig. 2a).\nIn addition, we compared IL-2 production by CD4+ T cells after CD3 and CD28 costimulation in the presence of IL-10 in active RA patients and in healthy controls. Similarly, IL-2 production was not affected by 1 ng/ml IL-10 in RA patients (percentage decrease, -2.1 ± 13.8%), while it was significantly reduced in healthy controls (61.1 ± 13.7%; P \u003c 0.05). Taken together, these results indicate that RA CD4+ T cells become less susceptible to the immunoregulatory effect of IL-10 during the active phase."}
bionlp-st-ge-2016-test-tees
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to IL-10 inhibition of IFN-γ production in RA CD4+ T cells\nThe CD28 costimulatory pathway is crucial for effective antigen-specific T-cell cytokine production, and IL-10 can directly suppress this response by inhibiting CD28 tyrosine phosphorylation and binding of phosphatidylinositol 3-kinase [24]. To evaluate the responsiveness of RA CD4+ T cells to IL-10, purified PB CD4+ T cells from three patients with active RA and from three healthy controls were stimulated by immobilized anti-CD3 antibody and anti-CD28 antibody with or without diluted concentrations of IL-10 for 36 hours, and IFN-γ production was measured by ELISA. As shown in Fig. 1, IFN-γ production by activated normal CD4+ T cells was mostly inhibited at concentrations as low as 1 ng/ml IL-10. However, RA CD4+ T cells were able to produce significant amounts of IFN-γ in the presence of 1 ng/ml IL-10, and the maximal but not complete inhibition by IL-10 was obtained at 10–100 ng/ml.\nWe thus compared the levels of IFN-γ production by CD4+ T cells after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 in RA patients with active disease (multiple inflammatory joints, CRP level ≥ 10 mg/l) and inactive disease (in remission, CRP level \u003c 10 mg/l) [26] and in healthy controls. There were no statistically significant differences in IFN-γ production without IL-10 among these three groups (Fig. 2a), but the inhibitory effect of IL-10 on IFN-γ production was significantly limited in the active RA group as compared with the inactive RA group and healthy controls (percentage decrease: active RA, 2.9 ± 14.4%; inactive RA, 45.6 ± 14.4%; controls, 65.8 ± 7.9%) (Fig. 2b). As a consequence, CD4+ T cells from active RA patients produced higher levels of IFN-γ in the presence of 1 ng/ml IL-10 than did normal CD4+ T cells (Fig. 2a).\nIn addition, we compared IL-2 production by CD4+ T cells after CD3 and CD28 costimulation in the presence of IL-10 in active RA patients and in healthy controls. Similarly, IL-2 production was not affected by 1 ng/ml IL-10 in RA patients (percentage decrease, -2.1 ± 13.8%), while it was significantly reduced in healthy controls (61.1 ± 13.7%; P \u003c 0.05). Taken together, these results indicate that RA CD4+ T cells become less susceptible to the immunoregulatory effect of IL-10 during the active phase."}
test3
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to IL-10 inhibition of IFN-γ production in RA CD4+ T cells\nThe CD28 costimulatory pathway is crucial for effective antigen-specific T-cell cytokine production, and IL-10 can directly suppress this response by inhibiting CD28 tyrosine phosphorylation and binding of phosphatidylinositol 3-kinase [24]. To evaluate the responsiveness of RA CD4+ T cells to IL-10, purified PB CD4+ T cells from three patients with active RA and from three healthy controls were stimulated by immobilized anti-CD3 antibody and anti-CD28 antibody with or without diluted concentrations of IL-10 for 36 hours, and IFN-γ production was measured by ELISA. As shown in Fig. 1, IFN-γ production by activated normal CD4+ T cells was mostly inhibited at concentrations as low as 1 ng/ml IL-10. However, RA CD4+ T cells were able to produce significant amounts of IFN-γ in the presence of 1 ng/ml IL-10, and the maximal but not complete inhibition by IL-10 was obtained at 10–100 ng/ml.\nWe thus compared the levels of IFN-γ production by CD4+ T cells after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 in RA patients with active disease (multiple inflammatory joints, CRP level ≥ 10 mg/l) and inactive disease (in remission, CRP level \u003c 10 mg/l) [26] and in healthy controls. There were no statistically significant differences in IFN-γ production without IL-10 among these three groups (Fig. 2a), but the inhibitory effect of IL-10 on IFN-γ production was significantly limited in the active RA group as compared with the inactive RA group and healthy controls (percentage decrease: active RA, 2.9 ± 14.4%; inactive RA, 45.6 ± 14.4%; controls, 65.8 ± 7.9%) (Fig. 2b). As a consequence, CD4+ T cells from active RA patients produced higher levels of IFN-γ in the presence of 1 ng/ml IL-10 than did normal CD4+ T cells (Fig. 2a).\nIn addition, we compared IL-2 production by CD4+ T cells after CD3 and CD28 costimulation in the presence of IL-10 in active RA patients and in healthy controls. Similarly, IL-2 production was not affected by 1 ng/ml IL-10 in RA patients (percentage decrease, -2.1 ± 13.8%), while it was significantly reduced in healthy controls (61.1 ± 13.7%; P \u003c 0.05). Taken together, these results indicate that RA CD4+ T cells become less susceptible to the immunoregulatory effect of IL-10 during the active phase."}
testone
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to IL-10 inhibition of IFN-γ production in RA CD4+ T cells\nThe CD28 costimulatory pathway is crucial for effective antigen-specific T-cell cytokine production, and IL-10 can directly suppress this response by inhibiting CD28 tyrosine phosphorylation and binding of phosphatidylinositol 3-kinase [24]. To evaluate the responsiveness of RA CD4+ T cells to IL-10, purified PB CD4+ T cells from three patients with active RA and from three healthy controls were stimulated by immobilized anti-CD3 antibody and anti-CD28 antibody with or without diluted concentrations of IL-10 for 36 hours, and IFN-γ production was measured by ELISA. As shown in Fig. 1, IFN-γ production by activated normal CD4+ T cells was mostly inhibited at concentrations as low as 1 ng/ml IL-10. However, RA CD4+ T cells were able to produce significant amounts of IFN-γ in the presence of 1 ng/ml IL-10, and the maximal but not complete inhibition by IL-10 was obtained at 10–100 ng/ml.\nWe thus compared the levels of IFN-γ production by CD4+ T cells after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 in RA patients with active disease (multiple inflammatory joints, CRP level ≥ 10 mg/l) and inactive disease (in remission, CRP level \u003c 10 mg/l) [26] and in healthy controls. There were no statistically significant differences in IFN-γ production without IL-10 among these three groups (Fig. 2a), but the inhibitory effect of IL-10 on IFN-γ production was significantly limited in the active RA group as compared with the inactive RA group and healthy controls (percentage decrease: active RA, 2.9 ± 14.4%; inactive RA, 45.6 ± 14.4%; controls, 65.8 ± 7.9%) (Fig. 2b). As a consequence, CD4+ T cells from active RA patients produced higher levels of IFN-γ in the presence of 1 ng/ml IL-10 than did normal CD4+ T cells (Fig. 2a).\nIn addition, we compared IL-2 production by CD4+ T cells after CD3 and CD28 costimulation in the presence of IL-10 in active RA patients and in healthy controls. Similarly, IL-2 production was not affected by 1 ng/ml IL-10 in RA patients (percentage decrease, -2.1 ± 13.8%), while it was significantly reduced in healthy controls (61.1 ± 13.7%; P \u003c 0.05). Taken together, these results indicate that RA CD4+ T cells become less susceptible to the immunoregulatory effect of IL-10 during the active phase."}