Induction of IL-10-producing CD4+CD25+ T cells in animal model of collagen-induced arthritis by oral administration of type II collagen.
Induction of IL-10-producing CD4+CD25+ T cells in animal model of collagen-induced arthritis by oral administration of type II collagen.
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DOI：
10.1186/ar1169
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发表时间：
2004
影响因子：
4.9
通讯作者：
Kim HY
中科院分区：
文献类型：
--
作者：
Min SY;Hwang SY;Park KS;Lee JS;Lee KE;Kim KW;Jung YO;Koh HJ;Do JH;Kim H;Kim HY
长期以来，诱导口服耐受一直被认为是治疗包括类风湿关节炎(RA)在内的慢性自身免疫性疾病的一种有前途的方法。口服II型胶原(CII)已被证明可以改善RA患者的体征和症状，且没有麻烦的毒性。在胶原性关节炎(CIA)动物模型上，观察了血清中免疫球蛋白G亚群和T细胞对CII的增殖反应，以及产生IL-10的CD4+CD25+T细胞亚群的变化，以探讨口服抗原免疫抑制的机制。我们发现CIA小鼠的关节炎症在初次免疫CII后5周达到高峰，而在CIA诱导前反复口服CII的小鼠关节炎症明显减轻。与不耐受的CIA动物相比，喂食CII的小鼠血清IgG1升高，血清IgG2a降低。耐受组小鼠的T细胞对CII的增殖反应也受到抑制。耐受组小鼠外周血单个核细胞产生IL-10和转化生长因子-β的量增加，而免疫耐受组小鼠分离的T细胞经CII刺激后对干扰素-γ的诱导无反应。我们还观察到免疫耐受小鼠经CII刺激的脾T细胞中产生IL-10的CD4+CD25+亚群的诱导率更高。这些数据表明，当这些产生IL-10的CD4+CD25+T细胞在受影响的关节中遇到CII抗原时，它们会被激活，发挥抗炎作用。
Induction of oral tolerance has long been considered a promising approach to the treatment of chronic autoimmune diseases, including rheumatoid arthritis (RA). Oral administration of type II collagen (CII) has been proven to improve signs and symptoms in RA patients without troublesome toxicity. To investigate the mechanism of immune suppression mediated by orally administered antigen, we examined changes in serum IgG subtypes and T-cell proliferative responses to CII, and generation of IL-10-producing CD4+CD25+ T-cell subsets in an animal model of collagen-induced arthritis (CIA). We found that joint inflammation in CIA mice peaked at 5 weeks after primary immunization with CII, which was significantly less in mice tolerized by repeated oral feeding of CII before CIA induction. Mice that had been fed with CII also exhibited increased serum IgG1 and decreased serum IgG2a as compared with nontolerized CIA animals. The T-cell proliferative response to CII was suppressed in lymph nodes of tolerized mice also. Production of IL-10 and of transforming growth factor-β from mononuclear lymphocytes was increased in the tolerized animals, and CD4+ T cells isolated from tolerized mice did not respond with induction of IFN-γ when stimulated in vitro with CII. We also observed greater induction of IL-10-producing CD4+CD25+ subsets among CII-stimulated splenic T cells from tolerized mice. These data suggest that when these IL-10-producing CD4+CD25+ T cells encounter CII antigen in affected joints they become activated to exert an anti-inflammatory effect.
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DOI：
10.1073/pnas.91.14.6688
发表时间：
1994-07-05
影响因子：
11.1
作者：
FRIEDMAN, A;WEINER, HL
通讯作者：
WEINER, HL
影响因子：
6.4
作者：
Tsuji, NM;Mizumachi, K;Kurisaki, JI
通讯作者：
Kurisaki, JI
DOI：
10.1084/jem.20020590
发表时间：
2002-07-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Piccirillo CA;Letterio JJ;Thornton AM;McHugh RS;Mamura M;Mizuhara H;Shevach EM
通讯作者：
Shevach EM
影响因子：
4.4
作者：
Annacker, O;Burlen-Defranoux, O;Bandeira, A
通讯作者：
Bandeira, A
影响因子：
56.9
作者：
TRENTHAM, DE;DYNESIUSTRENTHAM, RA;WEINER, HL
通讯作者：
WEINER, HL