Th1 to Th2 immune deviation facilitates, but does not cause, islet allograft tolerance in mice.
Th1 to Th2 immune deviation facilitates, but does not cause, islet allograft tolerance in mice.
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Th1 向 Th2 免疫偏差促进但不会导致小鼠胰岛同种异体移植物耐受。
DOI：
10.1016/j.cyto.2010.06.007
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发表时间：
2010
期刊：
影响因子：
3.8
通讯作者：
Zheng,XinXiao
中科院分区：
文献类型：
--
作者：
Zhang,Dong;Sanchez-Fueyo,Alberto;Kawamoto,Kensaku;Alexopoulos,SophoclisP;Zhang,Wensheng;Zheng,XinXiao
据报道，在涉及有限 T 细胞克隆大小的情况下，Th1 到 Th2 免疫偏差可有效促进外周耐受，例如 T 细胞依赖性自身免疫和跨次要但非主要组织相容性障碍的移植。在这项研究中，我们测试了这样的假设：虽然 Th1 到 Th2 免疫偏差未能在 MHC 不匹配的胰岛同种异体移植模型中诱导耐受，但它可能会促进允许诱导耐受的状态。在这里，我们报告说，单独施用时，抗IL-12并不能预防胰岛同种异体移植物的急性排斥。然而，与 CTLA4/Fc 结合，抗 IL-12 极大地促进了三种 MHC 不匹配菌株组合的长期植入。同样，虽然非溶细胞性 IL-4/Fc（IL-4 的一种长效形式）单独给药时不能预防急性移植物排斥，但低剂量（而非高剂量）的 IL-4/Fc 与 CTLA4/Fc 协同作用，可诱导显着水平的胰岛同种异体移植耐受。此外，通过使用皮肤同种异体移植过继转移模型，我们表明抗IL-12和IL-4/Fc治疗诱导的这些效应与CD4+CD25+调节性T细胞的抑制特性的增强相关。因此，抗IL-12和低剂量IL-4/Fc通过增加CD4+CD25+调节性T细胞的免疫抑制效力，促进但不引起小鼠胰岛同种异体移植物耐受。
It has been reported that Th1 to Th2 immune deviation effectively promotes peripheral tolerance in situations involving a limited T cell clone size, such as T cell-dependent autoimmunity and transplantation across minor, but not major, histocompatibility barriers. In this study, we tested the hypothesis that while Th1 to Th2 immune deviation fails to induce tolerance in the MHC-mismatched islet allograft model, it may promote a state that is permissive for tolerance induction. Here, we report that anti-IL-12 did not prevent acute rejection of islet allografts when administered alone. In conjunction with CTLA4/Fc, however, anti-IL-12 greatly facilitated long-term engraftment in three MHC-mismatched strain combinations. Similarly, while non-cytolytic IL-4/Fc, a long-lasting form of IL-4, did not prevent acute graft rejection when administered alone, a low, but not a high, dose of IL-4/Fc synergized with CTLA4/Fc in inducing significant levels of islet allograft tolerance. Moreover, by using a skin allograft adoptive transfer model, we show that these effects induced by anti-IL-12 and IL-4/Fc treatment were associated with an enhancement of the suppressive properties of CD4+CD25+regulatory T cells. Thus, anti-IL-12 and low-dose IL-4/Fc facilitate, but do not cause, islet allograft tolerance in mice by increasing the immunosuppressive potency of CD4+CD25+regulatory T cells.