CD4+ regulatory T cells require CTLA-4 for the maintenance of systemic tolerance.
CD4+ regulatory T cells require CTLA-4 for the maintenance of systemic tolerance.
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DOI：
10.1084/jem.20081811
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发表时间：
2009-02-16
期刊：
影响因子：
--
通讯作者：
Chambers CA
中科院分区：
文献类型：
--
作者：
Friedline RH;Brown DS;Nguyen H;Kornfeld H;Lee J;Zhang Y;Appleby M;Der SD;Kang J;Chambers CA
细胞毒性T淋巴细胞抗原-4(CTLA-4)在负性调节T细胞反应中起重要作用，也参与了天然FOXP3+调节性T细胞的发育和功能。CTLA-4基因缺陷的小鼠会患上致命性、早发性淋巴增生性疾病。然而，同时含有CTLA-4缺陷和足够的骨髓来源细胞的嵌合小鼠不会发生疾病，这表明CTLA-4可以通过反式作用来维持T细胞的自我耐受。使用基因混合胚泡和BM嵌合体以及体内T细胞转移系统，我们证明了在体内，由CTLA-4充足的T细胞调节CTLA4TRAN是一个可逆的过程，需要具有不同TCR谱的FOXP3+调节性T细胞的持续存在。根据基因表达研究，调节性T细胞似乎并不直接作用于T细胞，这表明它们可能相反地调节抗原提呈细胞的刺激活动。这些结果表明，CTLA-4是FOXP3+调节性T细胞在体内发挥功能所必需的。
Cytotoxic T lymphocyte antigen-4 (CTLA-4) plays a critical role in negatively regulating T cell responses and has also been implicated in the development and function of natural FOXP3+ regulatory T cells. CTLA-4–deficient mice develop fatal, early onset lymphoproliferative disease. However, chimeric mice containing both CTLA-4–deficient and –sufficient bone marrow (BM)–derived cells do not develop disease, indicating that CTLA-4 can act in trans to maintain T cell self-tolerance. Using genetically mixed blastocyst and BM chimaeras as well as in vivo T cell transfer systems, we demonstrate that in vivo regulation of Ctla4−/− T cells in trans by CTLA-4–sufficient T cells is a reversible process that requires the persistent presence of FOXP3+ regulatory T cells with a diverse TCR repertoire. Based on gene expression studies, the regulatory T cells do not appear to act directly on T cells, suggesting they may instead modulate the stimulatory activities of antigen-presenting cells. These results demonstrate that CTLA-4 is absolutely required for FOXP3+ regulatory T cell function in vivo.
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DOI：
10.1084/jem.186.8.1223
发表时间：
1997-10-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Brocker T
通讯作者：
Brocker T
DOI：
10.1073/pnas.94.17.9296
发表时间：
1997-08-19
影响因子：
11.1
作者：
Chambers, CA;Cado, D;Allison, JP
通讯作者：
Allison, JP
影响因子：
30.5
作者：
Fallarino, F;Grohmann, U;Puccetti, P
通讯作者：
Puccetti, P
影响因子：
32.4
作者：
Gorelik, L;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
32.4
作者：
Li, Ming O.;Wan, Yisong Y.;Flavell, Richard A.
通讯作者：
Flavell, Richard A.