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bionlp-st-ge-2016-uniprot

bionlp-st-ge-2016-reference

2_test

{"project":"2_test","denotations":[{"id":"19646904-7595230-46582684","span":{"begin":445,"end":449},"obj":"7595230"},{"id":"19646904-7595228-46582684","span":{"begin":445,"end":449},"obj":"7595228"},{"id":"19646904-14557415-46582685","span":{"begin":2591,"end":2595},"obj":"14557415"},{"id":"19646904-10880840-46582685","span":{"begin":2591,"end":2595},"obj":"10880840"},{"id":"T10777","span":{"begin":445,"end":449},"obj":"7595230"},{"id":"T18378","span":{"begin":445,"end":449},"obj":"7595228"},{"id":"T24066","span":{"begin":2591,"end":2595},"obj":"14557415"},{"id":"T49812","span":{"begin":2591,"end":2595},"obj":"10880840"}],"text":"IL-12 and High Doses of Antigen Induce the Development of Th1 Cells Producing IL-10\nTo study the differentiation of Th1 cells coproducing IFN-γ and IL-10, we cultured purified TCR-transgenic DO11.10 naive CD4+ T cells with purified DCs as APCs and increasing doses of ovalbumin peptide 323-339 (OVA). Culture with high doses of antigen for 7 days gave rise to Th1 cells expressing IFN-γ upon restimulation (Constant et al., 1995; Hosken et al., 1995), but not IL-10 (Figure S1A available online). Culture with low antigen doses under the same conditions led to the differentiation of Th2 cells, which expressed both IL-4 and IL-10 upon restimulation (Figure S1A). Culture of naive CD4+ T cells in an APC-free system by stimulation with anti-CD3 and anti-CD28 antibodies in the presence of IL-12 resulted in IFN-γ-producing Th1 cells, a proportion of which coproduced IL-10, as did Th2 cells resulting from culture in IL-4 (Figure S1B).\nTo investigate whether the lack of IL-10 produced by Th1 cells resulted from inhibition of IL-10 production by DCs and high antigen dose or alternatively required IL-12, we cultured naive CD4+ T cells with increasing doses of antigen presented by DC in the presence of IL-12. At low doses of antigen, IL-12 abrogated the development of Th2 cells and induced IFN-γ expression but only low levels of IL-10 expression, suggesting that IL-12 per se was not sufficient to induce significant IL-10 production in Th1 cells (Figure 1A). Strikingly, as the antigen dose was increased, Th1 populations driven with IL-12 now contained higher numbers of IL-10-producing cells (Figure 1A) and produced more IL-10 protein upon restimulation (Figures 1A and 1B). Thus, the development of Th1 cells producing IL-10 required both IL-12 and high doses of antigen. Th1 cells differentiated to produce large amounts of IL-10 and IFN-γ and lost their capacity to produce IL-2 (Figure 1B). Because the presence of IL-12 reduced the proliferation of CD4+ T cells at both high and low antigen doses (Table S1), and only the former showed IL-10 production, the development of high IL-10-producing cells is most likely not related to limited IL-2. Naive CD4+ T cells from DO11.10/recombination-activating gene 1 (Rag1)-deficient animals, cultured with high doses of antigen in the presence of IL-12, also resulted in IL-10 expression by Th1 cells, showing that this expression was not dependent on the presence of effector or memory T cells or Treg cells (Figure S2). Although it has been suggested that TGF-β can induce IL-10 in CD4+ T cells (Kitani et al., 2003; Schiott et al., 2000), we found that in developing Th1 and Th2 cells this was not the case (data not shown). In fact, neutralization of TGF-β led to increased IL-10 production by both T cell subsets (Figure S3). Thus, the development of IL-10-producing Th1 cells only depended on the presence of IL-12 together with high antigen dose and not on other soluble factors such as IL-2 or TGF-β or on the presence of other T cell types."}

pmc-enju-pas

bionlp-st-ge-2016-coref

{"project":"bionlp-st-ge-2016-coref","denotations":[{"id":"T3502","span":{"begin":2371,"end":2386},"obj":"Anaphor"},{"id":"T3503","span":{"begin":2333,"end":2343},"obj":"Antecedent"},{"id":"T3504","span":{"begin":2920,"end":2941},"obj":"Anaphor"},{"id":"T3505","span":{"begin":2950,"end":2954},"obj":"Antecedent"},{"id":"T3506","span":{"begin":2958,"end":2963},"obj":"Antecedent"}],"relations":[{"id":"R2723","pred":"boundBy","subj":"T3502","obj":"T3503"},{"id":"R2724","pred":"boundBy","subj":"T3504","obj":"T3505"},{"id":"R2725","pred":"boundBy","subj":"T3504","obj":"T3506"}],"namespaces":[{"prefix":"_base","uri":"https://bionlp.dbcls.jp/ontology/ge.owl#"}],"text":"IL-12 and High Doses of Antigen Induce the Development of Th1 Cells Producing IL-10\nTo study the differentiation of Th1 cells coproducing IFN-γ and IL-10, we cultured purified TCR-transgenic DO11.10 naive CD4+ T cells with purified DCs as APCs and increasing doses of ovalbumin peptide 323-339 (OVA). Culture with high doses of antigen for 7 days gave rise to Th1 cells expressing IFN-γ upon restimulation (Constant et al., 1995; Hosken et al., 1995), but not IL-10 (Figure S1A available online). Culture with low antigen doses under the same conditions led to the differentiation of Th2 cells, which expressed both IL-4 and IL-10 upon restimulation (Figure S1A). Culture of naive CD4+ T cells in an APC-free system by stimulation with anti-CD3 and anti-CD28 antibodies in the presence of IL-12 resulted in IFN-γ-producing Th1 cells, a proportion of which coproduced IL-10, as did Th2 cells resulting from culture in IL-4 (Figure S1B).\nTo investigate whether the lack of IL-10 produced by Th1 cells resulted from inhibition of IL-10 production by DCs and high antigen dose or alternatively required IL-12, we cultured naive CD4+ T cells with increasing doses of antigen presented by DC in the presence of IL-12. At low doses of antigen, IL-12 abrogated the development of Th2 cells and induced IFN-γ expression but only low levels of IL-10 expression, suggesting that IL-12 per se was not sufficient to induce significant IL-10 production in Th1 cells (Figure 1A). Strikingly, as the antigen dose was increased, Th1 populations driven with IL-12 now contained higher numbers of IL-10-producing cells (Figure 1A) and produced more IL-10 protein upon restimulation (Figures 1A and 1B). Thus, the development of Th1 cells producing IL-10 required both IL-12 and high doses of antigen. Th1 cells differentiated to produce large amounts of IL-10 and IFN-γ and lost their capacity to produce IL-2 (Figure 1B). Because the presence of IL-12 reduced the proliferation of CD4+ T cells at both high and low antigen doses (Table S1), and only the former showed IL-10 production, the development of high IL-10-producing cells is most likely not related to limited IL-2. Naive CD4+ T cells from DO11.10/recombination-activating gene 1 (Rag1)-deficient animals, cultured with high doses of antigen in the presence of IL-12, also resulted in IL-10 expression by Th1 cells, showing that this expression was not dependent on the presence of effector or memory T cells or Treg cells (Figure S2). Although it has been suggested that TGF-β can induce IL-10 in CD4+ T cells (Kitani et al., 2003; Schiott et al., 2000), we found that in developing Th1 and Th2 cells this was not the case (data not shown). In fact, neutralization of TGF-β led to increased IL-10 production by both T cell subsets (Figure S3). Thus, the development of IL-10-producing Th1 cells only depended on the presence of IL-12 together with high antigen dose and not on other soluble factors such as IL-2 or TGF-β or on the presence of other T cell types."}

bionlp-st-ge-2016-spacy-parsed

GO-BP

{"project":"GO-BP","denotations":[{"id":"T4162","span":{"begin":43,"end":54},"obj":"http://purl.obolibrary.org/obo/GO_0032502"},{"id":"T4163","span":{"begin":1257,"end":1268},"obj":"http://purl.obolibrary.org/obo/GO_0032502"},{"id":"T4164","span":{"begin":1694,"end":1705},"obj":"http://purl.obolibrary.org/obo/GO_0032502"},{"id":"T4165","span":{"begin":2072,"end":2083},"obj":"http://purl.obolibrary.org/obo/GO_0032502"},{"id":"T4166","span":{"begin":2797,"end":2808},"obj":"http://purl.obolibrary.org/obo/GO_0032502"},{"id":"T4167","span":{"begin":176,"end":179},"obj":"http://purl.obolibrary.org/obo/GO_0006283"},{"id":"T4168","span":{"begin":1027,"end":1043},"obj":"http://purl.obolibrary.org/obo/GO_0032653"},{"id":"T4169","span":{"begin":1422,"end":1438},"obj":"http://purl.obolibrary.org/obo/GO_0032653"},{"id":"T4170","span":{"begin":2050,"end":2066},"obj":"http://purl.obolibrary.org/obo/GO_0032653"},{"id":"T4171","span":{"begin":2734,"end":2750},"obj":"http://purl.obolibrary.org/obo/GO_0032653"},{"id":"T4172","span":{"begin":1027,"end":1043},"obj":"http://purl.obolibrary.org/obo/GO_0032613"},{"id":"T4173","span":{"begin":1422,"end":1438},"obj":"http://purl.obolibrary.org/obo/GO_0032613"},{"id":"T4174","span":{"begin":2050,"end":2066},"obj":"http://purl.obolibrary.org/obo/GO_0032613"},{"id":"T4175","span":{"begin":2734,"end":2750},"obj":"http://purl.obolibrary.org/obo/GO_0032613"},{"id":"T4176","span":{"begin":1786,"end":1806},"obj":"http://purl.obolibrary.org/obo/GO_0030154"},{"id":"T4177","span":{"begin":2436,"end":2442},"obj":"http://purl.obolibrary.org/obo/GO_0007613"}],"text":"IL-12 and High Doses of Antigen Induce the Development of Th1 Cells Producing IL-10\nTo study the differentiation of Th1 cells coproducing IFN-γ and IL-10, we cultured purified TCR-transgenic DO11.10 naive CD4+ T cells with purified DCs as APCs and increasing doses of ovalbumin peptide 323-339 (OVA). Culture with high doses of antigen for 7 days gave rise to Th1 cells expressing IFN-γ upon restimulation (Constant et al., 1995; Hosken et al., 1995), but not IL-10 (Figure S1A available online). Culture with low antigen doses under the same conditions led to the differentiation of Th2 cells, which expressed both IL-4 and IL-10 upon restimulation (Figure S1A). Culture of naive CD4+ T cells in an APC-free system by stimulation with anti-CD3 and anti-CD28 antibodies in the presence of IL-12 resulted in IFN-γ-producing Th1 cells, a proportion of which coproduced IL-10, as did Th2 cells resulting from culture in IL-4 (Figure S1B).\nTo investigate whether the lack of IL-10 produced by Th1 cells resulted from inhibition of IL-10 production by DCs and high antigen dose or alternatively required IL-12, we cultured naive CD4+ T cells with increasing doses of antigen presented by DC in the presence of IL-12. At low doses of antigen, IL-12 abrogated the development of Th2 cells and induced IFN-γ expression but only low levels of IL-10 expression, suggesting that IL-12 per se was not sufficient to induce significant IL-10 production in Th1 cells (Figure 1A). Strikingly, as the antigen dose was increased, Th1 populations driven with IL-12 now contained higher numbers of IL-10-producing cells (Figure 1A) and produced more IL-10 protein upon restimulation (Figures 1A and 1B). Thus, the development of Th1 cells producing IL-10 required both IL-12 and high doses of antigen. Th1 cells differentiated to produce large amounts of IL-10 and IFN-γ and lost their capacity to produce IL-2 (Figure 1B). Because the presence of IL-12 reduced the proliferation of CD4+ T cells at both high and low antigen doses (Table S1), and only the former showed IL-10 production, the development of high IL-10-producing cells is most likely not related to limited IL-2. Naive CD4+ T cells from DO11.10/recombination-activating gene 1 (Rag1)-deficient animals, cultured with high doses of antigen in the presence of IL-12, also resulted in IL-10 expression by Th1 cells, showing that this expression was not dependent on the presence of effector or memory T cells or Treg cells (Figure S2). Although it has been suggested that TGF-β can induce IL-10 in CD4+ T cells (Kitani et al., 2003; Schiott et al., 2000), we found that in developing Th1 and Th2 cells this was not the case (data not shown). In fact, neutralization of TGF-β led to increased IL-10 production by both T cell subsets (Figure S3). Thus, the development of IL-10-producing Th1 cells only depended on the presence of IL-12 together with high antigen dose and not on other soluble factors such as IL-2 or TGF-β or on the presence of other T cell types."}

GO-MF

GO-CC

sentences

events-check-again

bionlp-st-ge-2016-reference-tees

test2

PMC:2791889 / 5900-8905 JSONTXT

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PMC:2791889 / 5900-8905 JSON TXT