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首页> 外文期刊>Cytokine >Th1 to Th2 immune deviation facilitates, but does not cause, islet allograft tolerance in mice.
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Th1 to Th2 immune deviation facilitates, but does not cause, islet allograft tolerance in mice.

机译：Th1至Th2的免疫偏离促进但不引起小鼠胰岛同种异体移植耐受性。

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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.
机译：据报道，在涉及有限的T细胞克隆大小的情况下，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，Th1至Th2免疫偏离可有效促进外周耐受。在这项研究中，我们测试了以下假设：虽然在MHC不匹配的胰岛同种异体移植模型中Th1至Th2的免疫偏差无法诱导耐受，但它可能会促进允许耐受诱导的状态。在这里，我们报道抗IL-12不能单独给予胰岛同种异体移植急性排斥反应。但是，与CTLA4 / Fc结合使用时，抗IL-12大大促进了三种MHC不匹配菌株组合中的长期植入。类似地，虽然非细胞溶解性IL-4 / Fc（一种长效形式的IL-4）在单独给药时不能防止急性移植排斥，但低剂量但不是高剂量的CT-4协同作用的IL-4 / Fc / Fc诱导显着水平的胰岛同种异体移植耐受性。此外，通过使用同种异体皮肤过继转移模型，我们表明抗IL-12和IL-4 / Fc治疗诱导的这些作用与CD4（+）CD25（+）调节性T的抑制特性的增强有关。细胞。因此，抗IL-12和低剂量IL-4 / Fc可通过增加CD4（+）CD25（+）调节性T细胞的免疫抑制能力来促进小鼠胰岛同种异体耐受，但不会引起胰岛同种异体移植耐受。

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