IL-10-producing T regulatory type 1 cells and oral tolerance
IL-10-producing T regulatory type 1 cells and oral tolerance
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DOI：
10.1196/annals.1309.031
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Roncarolo, MG
中科院分区：
文献类型：
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作者：
Battaglia, M;Gianfrani, C;Roncarolo, MG
口服耐受是由多种机制介导的，如T调节T细胞对抗原特异性效应T细胞的无能和/或主动抑制。在CD4(+)Tr细胞中，T调节性1型细胞(TR1)通过产生免疫抑制细胞因子IL-10和TGF-β来下调免疫反应。人TR1细胞可被IL-10+干扰素-α诱导分化，或在未成熟树突状细胞(DC)刺激后分化，或经免疫调节化合物刺激后产生耐受。在高剂量IL-10存在下，小鼠TR1细胞可以通过激活初始的CD4(+)T细胞在体外被诱导分化。几种诱导口服耐受的方案，包括口服IL-10抗原，已被证明能诱导抗原特异性TR1细胞，抑制对自身抗原、过敏原和食物抗原的不受欢迎的免疫反应。总体而言，这些数据表明，产生IL-10的TR1细胞在诱导口服和全身耐受方面发挥着核心作用。
Oral tolerance is mediated by multiple mechanisms such as anergy and/or active suppression of antigen-specific effector T cells by T regulatory Tr) cells. Among the CD4(+) Tr cells, T regulatory type 1 cells (Tr1) have been shown to downmodulate immune responses through production of the immunosuppressive cytokines IL-10 and TGF-beta. Human Tr1 cells can be induced to differentiate in vitro by IL-10 + IFN-alpha or after stimulation by immature dendritic cells (DCs) or DCs rendered tolerogenic by exposure to immunomodulatory compounds. Murine Tr1 cells can be induced to differentiate in vitro by activating naive CD4(+) T cells in the presence of high doses of IL-10. Several protocols for induction of oral tolerance, including oral administration of the antigen with IL-10, have been shown to induce antigen-specific Tr1 cells that suppress undesired immune responses toward self-antigens, allergens, and food antigens. Overall, these data demonstrate that IL-10-producing Tr1 cells play a central role in the induction of oral as well as systemic tolerance.