CD62L- memory T cells enhance T-cell regeneration after allogeneic stem cell transplantation by eliminating host resistance in mice
CD62L- memory T cells enhance T-cell regeneration after allogeneic stem cell transplantation by eliminating host resistance in mice
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DOI：
10.1182/blood-2011-03-342055
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发表时间：
2012-06-28
期刊：
影响因子：
20.3
通讯作者：
Chen, Benny J.
中科院分区：
文献类型：
--
作者：
Zhang, Jifeng;Barefoot, Brice E.;Chen, Benny J.
异基因造血细胞移植的一个主要挑战是如何转移T细胞免疫而不引起移植物抗宿主病（GVHD）。效应记忆T细胞（CD 62 L（-））是一种可能解决这一挑战的细胞亚群，因为它们不会诱导GVHD。在这里，我们研究了CD 62 L（-）T细胞如何促进移植后T细胞的表型和功能重建。在转移到同种异体受体中时，CD 62 L（-）T细胞被激活并表达多种细胞因子和细胞毒性分子。CD 62 L（-）T细胞能够耗尽宿主抗辐射T细胞并促进造血移植，从而增强从头T细胞再生。使用肿瘤和流感病毒攻击模型，在CD 62 L（-）T细胞受体中证实了增强的功能性免疫重建。尽管CD 62 L（-）T细胞能够对同种异体抗原产生应答并耗尽GVHD受体中的宿主放射抗性免疫细胞，但同种异体反应性CD 62 L（-）T细胞随着时间的推移失去反应性，并最终由于延长的抗原暴露而对同种异体抗原产生耐受性，这表明CD 62 L（-）T细胞能够消除宿主抗性而不引起GVHD的机制。这些数据进一步强调了CD 62 L（-）T细胞的独特特性及其在临床造血细胞移植中的潜在应用。（血。2012;119（26）：6344-6353）
A major challenge in allogeneic hematopoietic cell transplantation is how to transfer T-cell immunity without causing graft-versus-host disease (GVHD). Effector memory T cells (CD62L(-)) are a cell subset that can potentially address this challenge because they do not induce GVHD. Here, we investigated how CD62L(-) T cells contributed to phenotypic and functional T-cell reconstitution after transplantation. On transfer into allogeneic recipients, CD62L(-) T cells were activated and ex-pressed multiple cytokines and cytotoxic molecules. CD62L(-) T cells were able to deplete host radioresistant T cells and facilitate hematopoietic engraftment, resulting in enhanced de novo T-cell regeneration. Enhanced functional immune reconstitution was demonstrated in CD62L(-) T-cell recipients using a tumor and an influenza virus challenge model. Even though CD62L(-) T cells are able to respond to alloantigens and deplete host radioresistant immune cells in GVHD recipients, alloreactive CD62L(-) T cells lost the reactivity over time and were eventually tolerant to alloantigens as a result of prolonged antigen exposure, suggesting a mechanism by which CD62L(-) T cells were able to eliminate host resistance without causing GVHD. These data further highlight the unique characteristics of CD62L(-) T cells and their potential applications in clinical hematopoietic cell transplantation. (Blood. 2012;119(26):6344-6353)