Natural CD8+CD122+T Cells Are More Potent in Suppression of Allograft Rejection Than CD4+CD25+Regulatory T Cells
Natural CD8+CD122+T Cells Are More Potent in Suppression of Allograft Rejection Than CD4+CD25+Regulatory T Cells
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DOI：
10.1111/ajt.12515
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发表时间：
2014-01-01
影响因子：
8.8
通讯作者：
Li, X. C.
中科院分区：
文献类型：
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作者：
Dai, Z.;Zhang, S.;Li, X. C.
尽管对CD4+CD25+调节性T细胞(Tregs)进行了广泛的研究，但在免疫活性野生型(WT)动物模型中，它们在过继转移治疗中的应用仍然不是最理想的。因此，寻找更有效的Tregs具有潜在的临床应用价值已迫在眉睫。越来越多的证据表明，自然产生的CD8+CD122+T细胞也是树突状细胞。然而，它们在同种异体移植排斥反应中的抑制、抑制的效率和潜在的机制仍不清楚。利用小鼠同种异体移植模型，我们在这里报道了CD8+CD122+Tregs实际上比它们的CD4+CD25+同种异体更有效地抑制同种异体移植排斥反应，并经历了更快的动态平衡增殖。此外，它们在体外产生更多的IL-10，并更有效地抑制T细胞的增殖。在体内、体外，CD8+CD122+Tregs和CD8+CD25+Tregs中IL-10的缺乏导致它们的抑制作用减弱但相同，提示CD8+CD122+Tregs对IL-10的抑制作用比CD4+CD25+Tregs更有效。重要的是，CD8+CD122+Tregs的转移和重组IL-15的应用显著延长了WT小鼠同种异体移植物的存活时间。因此，我们第一次证明，自然产生的CD8+CD122+Tregs不仅抑制同种异体移植排斥反应，而且比它们的CD4+CD25+Tregs更有效地发挥这种抑制作用。这一新发现可能对诱导耐受具有重要意义。在寻找更有效的调节性T细胞亚群的过程中，作者发现自然产生的CD8+CD122+T细胞比传统的CD4+CD25+调节性T细胞更有效地抑制同种异体移植排斥反应。见第7页Lerret和Luo的社论。
Despite extensive studies on CD4+CD25+ regulatory T cells (Tregs), their application in adoptive transfer therapies is still not optimal in immune-competent wild-type (WT) animal models. Therefore, it is compelling to search for more potent Tregs for potential clinical application. Mounting evidence has shown that naturally occurring CD8+CD122+ T cells are also Tregs. However, their suppression in allograft rejection, efficiency in suppression and underlying mechanisms remain unclear. Using a murine allotransplantation model, we reported here that CD8+CD122+ Tregs were actually more potent in suppression of allograft rejection and underwent more rapid homeostatic proliferation than their CD4+CD25+ counterparts. Moreover, they produced more IL-10 and were more potent in suppressing T cell proliferation in vitro. Deficiency in IL-10 in CD4+CD25+ and CD8+CD122+ Tregs resulted in their reduced but equal suppression in vivo and in vitro, suggesting that IL-10 is responsible for more effective suppression by CD8+CD122+ than CD4+CD25+ Tregs. Importantly, transfer of CD8+CD122+ Tregs together with the administration of recombinant IL-15 significantly prolonged allograft survival in WT mice. Thus, for the first time, we demonstrate that naturally arising CD8+CD122+ Tregs not only inhibit allograft rejection but also exert this suppression more potently than their CD4+CD25+ counterparts. This novel finding may have important implications for tolerance induction.In search of more efficient subsets of regulatory T cells, the authors find that naturally arising CD8+CD122+ T cells are more potent suppressors of allograft rejection than conventional CD4+CD25+ regulatory T cells. See editorial by Lerret and Luo on page 7.