Suppression of allograft rejection by CD8+CD122+PD-1+ Tregs is dictated by their Fas ligand-initiated killing of effector T cells versus Fas-mediated own apoptosis.
Suppression of allograft rejection by CD8+CD122+PD-1+ Tregs is dictated by their Fas ligand-initiated killing of effector T cells versus Fas-mediated own apoptosis.
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CD8 CD122 PD-1 Tregs 对同种异体移植排斥的抑制取决于其 Fas 配体启动的效应 T 细胞杀伤与 Fas 介导的自身凋亡
DOI：
10.18632/oncotarget.15551
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发表时间：
2017-04-11
期刊：
影响因子：
--
通讯作者：
Dai Z
中科院分区：
文献类型：
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作者：
Liu H;Wang Y;Zeng Q;Zeng YQ;Liang CL;Qiu F;Nie H;Dai Z
越来越多的证据表明，自然产生的CD8 + CD122 + T细胞是调节性T细胞（Tregs），可抑制自身免疫和同种免疫。我们先前已经表明，CD8 + CD122 + PD - 1 + Tregs不仅抑制同种异体移植排斥反应，而且在抑制作用上比常规的CD4 + CD25 + Tregs更强。然而，它们抑制同种免疫的潜在机制尚未完全清楚。在淋巴细胞缺失的小鼠过继性T细胞转移模型中，我们发现CD8 + CD122 + PD - 1 + Tregs对皮肤同种异体移植排斥反应的抑制主要依赖于其Fas配体的表达，因为Fas配体缺失或用抗体阻断它，在很大程度上消除了它们对转移T细胞介导的同种异体移植排斥反应的抑制作用。当效应T细胞缺乏Fas受体时，它们的抑制作用也大多被逆转。实际上，这些FasL + Tregs在体外以Fas / FasL依赖的方式诱导T细胞凋亡。然而，它们在体外对T细胞增殖的抑制依赖于IL - 10，而不是FasL表达。此外，在野生型小鼠中，如果Tregs缺乏Fas受体或者受体接受重组IL - 15，过继性转移CD8 + CD122 + PD - 1 + Tregs也能显著延长同种异体移植物的存活时间，因为这两种措施协同扩增了受体中过继转移的Tregs。因此，这项研究可能对临床移植中的Treg疗法具有重要意义。
Mounting evidence has shown that naturally occurring CD8+CD122+ T cells are regulatory T cells (Tregs) that suppress both autoimmunity and alloimmunity. We have previously shown that CD8+CD122+PD-1+ Tregs not only suppress allograft rejection, but also are more potent in suppression than conventional CD4+CD25+ Tregs. However, the mechanisms underlying their suppression of alloimmunity are not well understood. In an adoptive T-cell transfer model of mice lacking lymphocytes, we found that suppression of skin allograft rejection by CD8+CD122+PD-1+ Tregs was mostly dependent on their expression of Fas ligand as either lacking Fas ligand or blocking it with antibodies largely abolished their suppression of allograft rejection mediated by transferred T cells. Their suppression was also mostly reversed when effector T cells lacked Fas receptor. Indeed, these FasL+ Tregs induced T cell apoptosis in vitro in a Fas/FasL-dependent manner. However, their suppression of T cell proliferation in vitro was dependent on IL-10, but not FasL expression. Furthermore, adoptive transfer of CD8+CD122+PD-1+ Tregs significantly extended allograft survival even in wild-type mice if Tregs lacked Fas receptor or if recipients received recombinant IL-15, as these two measures synergistically expanded adoptively-transferred Tregs in recipients. Thus, this study may have important implications for Treg therapies in clinical transplantation.