比较 Th1、Th2 和 Th17 细胞对 Fas 介导的细胞凋亡的敏感性。
Comparison of sensitivity of Th1, Th2, and Th17 cells to Fas-mediated apoptosis.
机构信息
Research Service, Harry S. Truman Memorial VA Hospital, Department of Internal Medicine, School of Medicine, University of Missouri, Columbia, Missouri, USA.
出版信息
J Leukoc Biol. 2010 Jun;87(6):1019-28. doi: 10.1189/jlb.0509352.
Following activation through the TCR, CD4+ T cells can differentiate into three major subsets: Th1, Th2, and Th17 cells. IL-17-secreting Th17 cells play an important role in the pathogenesis of several autoimmune diseases and in immune responses to pathogens, but little is known about the regulation of apoptosis in Th17 cells. In this study, the sensitivity of in vitro-polarized Th1, Th2, and Th17 cells to Fas-mediated apoptosis was compared directly by different methods. The order of sensitivity of T cell subsets to Fas-mediated apoptosis is: Th1 > Th17 > Th2. The greater sensitivity of Th17 cells to Fas-mediated apoptosis compared with Th2 cells correlated with their higher expression of FasL and comparable expression of the antiapoptotic molecule FLIP. The decreased sensitivity of Th17 compared with Th1 cells correlated with the higher expression of FLIP by Th17 cells. Transgenic overexpression of FLIP in T cells protected all three subsets from Fas-mediated apoptosis. These findings provide new knowledge for understanding how survival of different subsets of T cells is regulated.
CD4+T 细胞在 TCR 激活后可以分化为三个主要亚群：Th1、Th2 和 Th17 细胞。分泌 IL-17 的 Th17 细胞在几种自身免疫性疾病的发病机制和对病原体的免疫反应中起着重要作用，但对于 Th17 细胞凋亡的调节知之甚少。在这项研究中，通过不同的方法直接比较了体外极化的 Th1、Th2 和 Th17 细胞对 Fas 介导的细胞凋亡的敏感性。T 细胞亚群对 Fas 介导的细胞凋亡的敏感性顺序为：Th1＞Th17＞Th2。与 Th2 细胞相比，Th17 细胞对 Fas 介导的细胞凋亡的敏感性更高，这与它们更高表达 FasL 和可比表达抗凋亡分子 FLIP 有关。与 Th1 细胞相比，Th17 细胞的敏感性降低与 Th17 细胞中更高表达的 FLIP 有关。T 细胞中 FLIP 的转基因过表达可防止三种亚群都受到 Fas 介导的凋亡。这些发现为了解不同 T 细胞亚群的存活是如何调节的提供了新的知识。
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