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Blood CD4+ T cells from RA patients contained higher levels of suppressor of cytokine signaling 1 but lower levels of suppressor of cytokine signaling 3 mRNA compared with control CD4+ T cells, as determined by real-time PCR. These results indicate that RA CD4+ T cells become resistant to the immunosuppressive effect of IL-10 before migration into synovial tissue, and this impaired IL-10 signaling may be associated with sustained signal transducer and activator of transcription 3 activation and suppressor of cytokine signaling 1 induction."}

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We found that peripheral blood CD4+ T cells from patients with active rheumatoid arthritis (RA) were able to produce greater amounts of interferon gamma after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 than were normal control CD4+ T cells, although their surface expression of the type 1 IL-10 receptor was increased. The phosphorylation of signal transducer and activator of transcription 3 was sustained in both blood and synovial tissue CD4+ T cells of RA, but it was not augmented by the presence of 1 ng/ml IL-10. Sera from RA patients induced signal transducer and activator of transcription 3 phosphorylation in normal CD4+ T cells, which was mostly abolished by neutralizing anti-IL-6 antibody. Preincubation of normal CD4+ T cells with IL-6 reduced IL-10-mediated inhibition of interferon gamma production. Blood CD4+ T cells from RA patients contained higher levels of suppressor of cytokine signaling 1 but lower levels of suppressor of cytokine signaling 3 mRNA compared with control CD4+ T cells, as determined by real-time PCR. These results indicate that RA CD4+ T cells become resistant to the immunosuppressive effect of IL-10 before migration into synovial tissue, and this impaired IL-10 signaling may be associated with sustained signal transducer and activator of transcription 3 activation and suppressor of cytokine signaling 1 induction."}

{"project":"bionlp-st-ge-2016-test-proteins","denotations":[{"id":"T997","span":{"begin":1452,"end":1486},"obj":"Protein"},{"id":"T996","span":{"begin":1386,"end":1436},"obj":"Protein"},{"id":"T971","span":{"begin":0,"end":5},"obj":"Protein"},{"id":"T972","span":{"begin":94,"end":98},"obj":"Protein"},{"id":"T973","span":{"begin":149,"end":152},"obj":"Protein"},{"id":"T974","span":{"begin":254,"end":270},"obj":"Protein"},{"id":"T975","span":{"begin":285,"end":289},"obj":"Protein"},{"id":"T976","span":{"begin":331,"end":336},"obj":"Protein"},{"id":"T977","span":{"begin":362,"end":365},"obj":"Protein"},{"id":"T978","span":{"begin":417,"end":438},"obj":"Protein"},{"id":"T979","span":{"begin":477,"end":527},"obj":"Protein"},{"id":"T980","span":{"begin":576,"end":579},"obj":"Protein"},{"id":"T981","span":{"begin":648,"end":653},"obj":"Protein"},{"id":"T982","span":{"begin":685,"end":735},"obj":"Protein"},{"id":"T983","span":{"begin":762,"end":765},"obj":"Protein"},{"id":"T984","span":{"begin":824,"end":828},"obj":"Protein"},{"id":"T985","span":{"begin":863,"end":866},"obj":"Protein"},{"id":"T986","span":{"begin":881,"end":885},"obj":"Protein"},{"id":"T987","span":{"begin":894,"end":899},"obj":"Protein"},{"id":"T988","span":{"begin":923,"end":939},"obj":"Protein"},{"id":"T989","span":{"begin":958,"end":961},"obj":"Protein"},{"id":"T990","span":{"begin":1015,"end":1049},"obj":"Protein"},{"id":"T991","span":{"begin":1070,"end":1104},"obj":"Protein"},{"id":"T992","span":{"begin":1132,"end":1135},"obj":"Protein"},{"id":"T993","span":{"begin":1209,"end":1212},"obj":"Protein"},{"id":"T994","span":{"begin":1274,"end":1279},"obj":"Protein"},{"id":"T995","span":{"begin":1337,"end":1342},"obj":"Protein"}],"namespaces":[{"prefix":"_base","uri":"http://bionlp.dbcls.jp/ontology/ge.owl#"}],"text":"IL-10 has been shown to block the antigen-specific T-cell cytokine response by inhibiting the CD28 signaling pathway. We found that peripheral blood CD4+ T cells from patients with active rheumatoid arthritis (RA) were able to produce greater amounts of interferon gamma after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 than were normal control CD4+ T cells, although their surface expression of the type 1 IL-10 receptor was increased. The phosphorylation of signal transducer and activator of transcription 3 was sustained in both blood and synovial tissue CD4+ T cells of RA, but it was not augmented by the presence of 1 ng/ml IL-10. Sera from RA patients induced signal transducer and activator of transcription 3 phosphorylation in normal CD4+ T cells, which was mostly abolished by neutralizing anti-IL-6 antibody. Preincubation of normal CD4+ T cells with IL-6 reduced IL-10-mediated inhibition of interferon gamma production. Blood CD4+ T cells from RA patients contained higher levels of suppressor of cytokine signaling 1 but lower levels of suppressor of cytokine signaling 3 mRNA compared with control CD4+ T cells, as determined by real-time PCR. These results indicate that RA CD4+ T cells become resistant to the immunosuppressive effect of IL-10 before migration into synovial tissue, and this impaired IL-10 signaling may be associated with sustained signal transducer and activator of transcription 3 activation and suppressor of cytokine signaling 1 induction."}

{"project":"bionlp-st-ge-2016-uniprot","denotations":[{"id":"T1053","span":{"begin":277,"end":280},"obj":"http://www.uniprot.org/uniprot/P07766"},{"id":"T1052","span":{"begin":277,"end":280},"obj":"http://www.uniprot.org/uniprot/P04234"},{"id":"T1051","span":{"begin":277,"end":280},"obj":"http://www.uniprot.org/uniprot/P20963"},{"id":"T1050","span":{"begin":285,"end":289},"obj":"http://www.uniprot.org/uniprot/P10747"},{"id":"T1049","span":{"begin":94,"end":98},"obj":"http://www.uniprot.org/uniprot/P10747"},{"id":"T1036","span":{"begin":1337,"end":1342},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T1035","span":{"begin":1274,"end":1279},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T1034","span":{"begin":894,"end":899},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T1088","span":{"begin":1421,"end":1447},"obj":"http://www.uniprot.org/uniprot/P18847-3"},{"id":"T1087","span":{"begin":881,"end":885},"obj":"http://www.uniprot.org/uniprot/P05231"},{"id":"T1086","span":{"begin":824,"end":828},"obj":"http://www.uniprot.org/uniprot/P05231"},{"id":"T1085","span":{"begin":277,"end":280},"obj":"http://www.uniprot.org/uniprot/P09693"},{"id":"T1030","span":{"begin":0,"end":5},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T1031","span":{"begin":331,"end":336},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T1032","span":{"begin":424,"end":429},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T1033","span":{"begin":648,"end":653},"obj":"http://www.uniprot.org/uniprot/P22301"},{"id":"T1038","span":{"begin":254,"end":270},"obj":"http://www.uniprot.org/uniprot/P01579"},{"id":"T1039","span":{"begin":923,"end":939},"obj":"http://www.uniprot.org/uniprot/P01579"},{"id":"T1041","span":{"begin":149,"end":152},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T1042","span":{"begin":362,"end":365},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T1043","span":{"begin":576,"end":579},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T1044","span":{"begin":762,"end":765},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T1045","span":{"begin":863,"end":866},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T1046","span":{"begin":958,"end":961},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T1047","span":{"begin":1132,"end":1135},"obj":"http://www.uniprot.org/uniprot/P01730"},{"id":"T1048","span":{"begin":1209,"end":1212},"obj":"http://www.uniprot.org/uniprot/P01730"}],"namespaces":[{"prefix":"_base","uri":"http://www.uniprot.org/uniprot/"}],"text":"IL-10 has been shown to block the antigen-specific T-cell cytokine response by inhibiting the CD28 signaling pathway. We found that peripheral blood CD4+ T cells from patients with active rheumatoid arthritis (RA) were able to produce greater amounts of interferon gamma after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 than were normal control CD4+ T cells, although their surface expression of the type 1 IL-10 receptor was increased. The phosphorylation of signal transducer and activator of transcription 3 was sustained in both blood and synovial tissue CD4+ T cells of RA, but it was not augmented by the presence of 1 ng/ml IL-10. Sera from RA patients induced signal transducer and activator of transcription 3 phosphorylation in normal CD4+ T cells, which was mostly abolished by neutralizing anti-IL-6 antibody. Preincubation of normal CD4+ T cells with IL-6 reduced IL-10-mediated inhibition of interferon gamma production. Blood CD4+ T cells from RA patients contained higher levels of suppressor of cytokine signaling 1 but lower levels of suppressor of cytokine signaling 3 mRNA compared with control CD4+ T cells, as determined by real-time PCR. These results indicate that RA CD4+ T cells become resistant to the immunosuppressive effect of IL-10 before migration into synovial tissue, and this impaired IL-10 signaling may be associated with sustained signal transducer and activator of transcription 3 activation and suppressor of cytokine signaling 1 induction."}

{"project":"UBERON-AE","denotations":[{"id":"T437","span":{"begin":1311,"end":1317},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"T436","span":{"begin":569,"end":575},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"T435","span":{"begin":550,"end":555},"obj":"http://purl.obolibrary.org/obo/UBERON_0000178"},{"id":"T434","span":{"begin":143,"end":148},"obj":"http://purl.obolibrary.org/obo/UBERON_0000178"}],"text":"IL-10 has been shown to block the antigen-specific T-cell cytokine response by inhibiting the CD28 signaling pathway. We found that peripheral blood CD4+ T cells from patients with active rheumatoid arthritis (RA) were able to produce greater amounts of interferon gamma after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 than were normal control CD4+ T cells, although their surface expression of the type 1 IL-10 receptor was increased. The phosphorylation of signal transducer and activator of transcription 3 was sustained in both blood and synovial tissue CD4+ T cells of RA, but it was not augmented by the presence of 1 ng/ml IL-10. Sera from RA patients induced signal transducer and activator of transcription 3 phosphorylation in normal CD4+ T cells, which was mostly abolished by neutralizing anti-IL-6 antibody. Preincubation of normal CD4+ T cells with IL-6 reduced IL-10-mediated inhibition of interferon gamma production. Blood CD4+ T cells from RA patients contained higher levels of suppressor of cytokine signaling 1 but lower levels of suppressor of cytokine signaling 3 mRNA compared with control CD4+ T cells, as determined by real-time PCR. These results indicate that RA CD4+ T cells become resistant to the immunosuppressive effect of IL-10 before migration into synovial tissue, and this impaired IL-10 signaling may be associated with sustained signal transducer and activator of transcription 3 activation and suppressor of cytokine signaling 1 induction."}

{"project":"GO-BP","denotations":[{"id":"T912","span":{"begin":1421,"end":1434},"obj":"http://purl.obolibrary.org/obo/GO_0006351"},{"id":"T911","span":{"begin":720,"end":733},"obj":"http://purl.obolibrary.org/obo/GO_0006351"},{"id":"T910","span":{"begin":512,"end":525},"obj":"http://purl.obolibrary.org/obo/GO_0006351"},{"id":"T909","span":{"begin":736,"end":751},"obj":"http://purl.obolibrary.org/obo/GO_0016310"},{"id":"T908","span":{"begin":458,"end":473},"obj":"http://purl.obolibrary.org/obo/GO_0016310"},{"id":"T907","span":{"begin":424,"end":438},"obj":"http://purl.obolibrary.org/obo/GO_0004920"},{"id":"T906","span":{"begin":99,"end":116},"obj":"http://purl.obolibrary.org/obo/GO_0007165"},{"id":"T905","span":{"begin":58,"end":75},"obj":"http://purl.obolibrary.org/obo/GO_0034097"},{"id":"T904","span":{"begin":51,"end":66},"obj":"http://purl.obolibrary.org/obo/GO_0002369"},{"id":"T903","span":{"begin":1475,"end":1484},"obj":"http://purl.obolibrary.org/obo/GO_0023052"},{"id":"T902","span":{"begin":1343,"end":1352},"obj":"http://purl.obolibrary.org/obo/GO_0023052"},{"id":"T901","span":{"begin":1093,"end":1102},"obj":"http://purl.obolibrary.org/obo/GO_0023052"},{"id":"T900","span":{"begin":1038,"end":1047},"obj":"http://purl.obolibrary.org/obo/GO_0023052"},{"id":"T899","span":{"begin":99,"end":108},"obj":"http://purl.obolibrary.org/obo/GO_0023052"},{"id":"T897","span":{"begin":923,"end":950},"obj":"http://purl.obolibrary.org/obo/GO_0032689"},{"id":"T895","span":{"begin":923,"end":950},"obj":"http://purl.obolibrary.org/obo/GO_0032649"},{"id":"T893","span":{"begin":923,"end":950},"obj":"http://purl.obolibrary.org/obo/GO_0032609"},{"id":"T891","span":{"begin":923,"end":950},"obj":"http://purl.obolibrary.org/obo/GO_0032729"}],"text":"IL-10 has been shown to block the antigen-specific T-cell cytokine response by inhibiting the CD28 signaling pathway. We found that peripheral blood CD4+ T cells from patients with active rheumatoid arthritis (RA) were able to produce greater amounts of interferon gamma after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 than were normal control CD4+ T cells, although their surface expression of the type 1 IL-10 receptor was increased. The phosphorylation of signal transducer and activator of transcription 3 was sustained in both blood and synovial tissue CD4+ T cells of RA, but it was not augmented by the presence of 1 ng/ml IL-10. Sera from RA patients induced signal transducer and activator of transcription 3 phosphorylation in normal CD4+ T cells, which was mostly abolished by neutralizing anti-IL-6 antibody. Preincubation of normal CD4+ T cells with IL-6 reduced IL-10-mediated inhibition of interferon gamma production. Blood CD4+ T cells from RA patients contained higher levels of suppressor of cytokine signaling 1 but lower levels of suppressor of cytokine signaling 3 mRNA compared with control CD4+ T cells, as determined by real-time PCR. These results indicate that RA CD4+ T cells become resistant to the immunosuppressive effect of IL-10 before migration into synovial tissue, and this impaired IL-10 signaling may be associated with sustained signal transducer and activator of transcription 3 activation and suppressor of cytokine signaling 1 induction."}

{"project":"GO-CC","denotations":[{"id":"T1024","span":{"begin":829,"end":837},"obj":"http://purl.obolibrary.org/obo/GO_0042571"},{"id":"T1023","span":{"begin":829,"end":837},"obj":"http://purl.obolibrary.org/obo/GO_0019815"},{"id":"T1022","span":{"begin":1216,"end":1221},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T1021","span":{"begin":1139,"end":1144},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T1020","span":{"begin":965,"end":970},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T1019","span":{"begin":870,"end":875},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T1018","span":{"begin":769,"end":774},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T1017","span":{"begin":583,"end":588},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T1016","span":{"begin":369,"end":374},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T1015","span":{"begin":156,"end":161},"obj":"http://purl.obolibrary.org/obo/GO_0005623"}],"text":"IL-10 has been shown to block the antigen-specific T-cell cytokine response by inhibiting the CD28 signaling pathway. We found that peripheral blood CD4+ T cells from patients with active rheumatoid arthritis (RA) were able to produce greater amounts of interferon gamma after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 than were normal control CD4+ T cells, although their surface expression of the type 1 IL-10 receptor was increased. The phosphorylation of signal transducer and activator of transcription 3 was sustained in both blood and synovial tissue CD4+ T cells of RA, but it was not augmented by the presence of 1 ng/ml IL-10. Sera from RA patients induced signal transducer and activator of transcription 3 phosphorylation in normal CD4+ T cells, which was mostly abolished by neutralizing anti-IL-6 antibody. Preincubation of normal CD4+ T cells with IL-6 reduced IL-10-mediated inhibition of interferon gamma production. Blood CD4+ T cells from RA patients contained higher levels of suppressor of cytokine signaling 1 but lower levels of suppressor of cytokine signaling 3 mRNA compared with control CD4+ T cells, as determined by real-time PCR. These results indicate that RA CD4+ T cells become resistant to the immunosuppressive effect of IL-10 before migration into synovial tissue, and this impaired IL-10 signaling may be associated with sustained signal transducer and activator of transcription 3 activation and suppressor of cytokine signaling 1 induction."}

{"project":"GO-MF","denotations":[{"id":"T1013","span":{"begin":829,"end":837},"obj":"http://purl.obolibrary.org/obo/GO_0003823"},{"id":"T1012","span":{"begin":881,"end":885},"obj":"http://purl.obolibrary.org/obo/GO_0005138"},{"id":"T1011","span":{"begin":824,"end":828},"obj":"http://purl.obolibrary.org/obo/GO_0005138"},{"id":"T1010","span":{"begin":424,"end":438},"obj":"http://purl.obolibrary.org/obo/GO_0004920"},{"id":"T1009","span":{"begin":422,"end":426},"obj":"http://purl.obolibrary.org/obo/GO_0005149"},{"id":"T1008","span":{"begin":923,"end":939},"obj":"http://purl.obolibrary.org/obo/GO_0005133"},{"id":"T1007","span":{"begin":254,"end":270},"obj":"http://purl.obolibrary.org/obo/GO_0005133"},{"id":"T1005","span":{"begin":1337,"end":1342},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T1004","span":{"begin":1274,"end":1279},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T1003","span":{"begin":894,"end":899},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T1002","span":{"begin":648,"end":653},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T1001","span":{"begin":424,"end":429},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T1000","span":{"begin":331,"end":336},"obj":"http://purl.obolibrary.org/obo/GO_0005141"},{"id":"T999","span":{"begin":0,"end":5},"obj":"http://purl.obolibrary.org/obo/GO_0005141"}],"text":"IL-10 has been shown to block the antigen-specific T-cell cytokine response by inhibiting the CD28 signaling pathway. We found that peripheral blood CD4+ T cells from patients with active rheumatoid arthritis (RA) were able to produce greater amounts of interferon gamma after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 than were normal control CD4+ T cells, although their surface expression of the type 1 IL-10 receptor was increased. The phosphorylation of signal transducer and activator of transcription 3 was sustained in both blood and synovial tissue CD4+ T cells of RA, but it was not augmented by the presence of 1 ng/ml IL-10. Sera from RA patients induced signal transducer and activator of transcription 3 phosphorylation in normal CD4+ T cells, which was mostly abolished by neutralizing anti-IL-6 antibody. Preincubation of normal CD4+ T cells with IL-6 reduced IL-10-mediated inhibition of interferon gamma production. Blood CD4+ T cells from RA patients contained higher levels of suppressor of cytokine signaling 1 but lower levels of suppressor of cytokine signaling 3 mRNA compared with control CD4+ T cells, as determined by real-time PCR. These results indicate that RA CD4+ T cells become resistant to the immunosuppressive effect of IL-10 before migration into synovial tissue, and this impaired IL-10 signaling may be associated with sustained signal transducer and activator of transcription 3 activation and suppressor of cytokine signaling 1 induction."}

{"project":"sentences","denotations":[{"id":"T883","span":{"begin":0,"end":117},"obj":"Sentence"},{"id":"T884","span":{"begin":118,"end":453},"obj":"Sentence"},{"id":"T885","span":{"begin":454,"end":654},"obj":"Sentence"},{"id":"T886","span":{"begin":655,"end":838},"obj":"Sentence"},{"id":"T887","span":{"begin":839,"end":951},"obj":"Sentence"},{"id":"T888","span":{"begin":952,"end":1177},"obj":"Sentence"},{"id":"T889","span":{"begin":1178,"end":1497},"obj":"Sentence"},{"id":"T3","span":{"begin":0,"end":117},"obj":"Sentence"},{"id":"T4","span":{"begin":118,"end":453},"obj":"Sentence"},{"id":"T5","span":{"begin":454,"end":654},"obj":"Sentence"},{"id":"T6","span":{"begin":655,"end":838},"obj":"Sentence"},{"id":"T7","span":{"begin":839,"end":951},"obj":"Sentence"},{"id":"T8","span":{"begin":952,"end":1177},"obj":"Sentence"},{"id":"T9","span":{"begin":1178,"end":1497},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"IL-10 has been shown to block the antigen-specific T-cell cytokine response by inhibiting the CD28 signaling pathway. We found that peripheral blood CD4+ T cells from patients with active rheumatoid arthritis (RA) were able to produce greater amounts of interferon gamma after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 than were normal control CD4+ T cells, although their surface expression of the type 1 IL-10 receptor was increased. The phosphorylation of signal transducer and activator of transcription 3 was sustained in both blood and synovial tissue CD4+ T cells of RA, but it was not augmented by the presence of 1 ng/ml IL-10. Sera from RA patients induced signal transducer and activator of transcription 3 phosphorylation in normal CD4+ T cells, which was mostly abolished by neutralizing anti-IL-6 antibody. Preincubation of normal CD4+ T cells with IL-6 reduced IL-10-mediated inhibition of interferon gamma production. Blood CD4+ T cells from RA patients contained higher levels of suppressor of cytokine signaling 1 but lower levels of suppressor of cytokine signaling 3 mRNA compared with control CD4+ T cells, as determined by real-time PCR. These results indicate that RA CD4+ T cells become resistant to the immunosuppressive effect of IL-10 before migration into synovial tissue, and this impaired IL-10 signaling may be associated with sustained signal transducer and activator of transcription 3 activation and suppressor of cytokine signaling 1 induction."}

{"project":"ICD10","denotations":[{"id":"T1026","span":{"begin":188,"end":208},"obj":"http://purl.bioontology.org/ontology/ICD10/M06.9"},{"id":"T1028","span":{"begin":199,"end":208},"obj":"http://purl.bioontology.org/ontology/ICD10/M13.9"}],"text":"IL-10 has been shown to block the antigen-specific T-cell cytokine response by inhibiting the CD28 signaling pathway. We found that peripheral blood CD4+ T cells from patients with active rheumatoid arthritis (RA) were able to produce greater amounts of interferon gamma after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 than were normal control CD4+ T cells, although their surface expression of the type 1 IL-10 receptor was increased. The phosphorylation of signal transducer and activator of transcription 3 was sustained in both blood and synovial tissue CD4+ T cells of RA, but it was not augmented by the presence of 1 ng/ml IL-10. Sera from RA patients induced signal transducer and activator of transcription 3 phosphorylation in normal CD4+ T cells, which was mostly abolished by neutralizing anti-IL-6 antibody. Preincubation of normal CD4+ T cells with IL-6 reduced IL-10-mediated inhibition of interferon gamma production. Blood CD4+ T cells from RA patients contained higher levels of suppressor of cytokine signaling 1 but lower levels of suppressor of cytokine signaling 3 mRNA compared with control CD4+ T cells, as determined by real-time PCR. These results indicate that RA CD4+ T cells become resistant to the immunosuppressive effect of IL-10 before migration into synovial tissue, and this impaired IL-10 signaling may be associated with sustained signal transducer and activator of transcription 3 activation and suppressor of cytokine signaling 1 induction."}

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We found that peripheral blood CD4+ T cells from patients with active rheumatoid arthritis (RA) were able to produce greater amounts of interferon gamma after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 than were normal control CD4+ T cells, although their surface expression of the type 1 IL-10 receptor was increased. The phosphorylation of signal transducer and activator of transcription 3 was sustained in both blood and synovial tissue CD4+ T cells of RA, but it was not augmented by the presence of 1 ng/ml IL-10. Sera from RA patients induced signal transducer and activator of transcription 3 phosphorylation in normal CD4+ T cells, which was mostly abolished by neutralizing anti-IL-6 antibody. Preincubation of normal CD4+ T cells with IL-6 reduced IL-10-mediated inhibition of interferon gamma production. 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has been shown to block the antigen-specific T-cell cytokine response by inhibiting the CD28 signaling pathway. We found that peripheral blood CD4+ T cells from patients with active rheumatoid arthritis (RA) were able to produce greater amounts of interferon gamma after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 than were normal control CD4+ T cells, although their surface expression of the type 1 IL-10 receptor was increased. The phosphorylation of signal transducer and activator of transcription 3 was sustained in both blood and synovial tissue CD4+ T cells of RA, but it was not augmented by the presence of 1 ng/ml IL-10. Sera from RA patients induced signal transducer and activator of transcription 3 phosphorylation in normal CD4+ T cells, which was mostly abolished by neutralizing anti-IL-6 antibody. Preincubation of normal CD4+ T cells with IL-6 reduced IL-10-mediated inhibition of interferon gamma production. Blood CD4+ T cells from RA patients contained higher levels of suppressor of cytokine signaling 1 but lower levels of suppressor of cytokine signaling 3 mRNA compared with control CD4+ T cells, as determined by real-time PCR. These results indicate that RA CD4+ T cells become resistant to the immunosuppressive effect of IL-10 before migration into synovial tissue, and this impaired IL-10 signaling may be associated with sustained signal transducer and activator of transcription 3 activation and suppressor of cytokine signaling 1 induction."}

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