Modulation of Fas-dependent apoptosis: A dynamic process controlling both the persistence and death of CD4 regulatory T cells and effector T cells
Modulation of Fas-dependent apoptosis: A dynamic process controlling both the persistence and death of CD4 regulatory T cells and effector T cells
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DOI：
10.4049/jimmunol.169.2.750
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发表时间：
2002-07-15
影响因子：
4.4
通讯作者：
Papiernik, M
中科院分区：
文献类型：
--
作者：
Banz, A;Pontoux, C;Papiernik, M
我们先前已经证明，调节性CD 25（+）CD 4（+）T细胞对体内病毒超抗原诱导的克隆缺失具有抗性。在这项工作中，我们报告了分离的CD 25（+）CD 4（+）T细胞在体外激活的抗CD 3抗体是抵抗Fas诱导的凋亡，相反，他们的CD 25（-）CD 4（+）对应。CD 25（+）CD 4（+）T细胞对Fas依赖性激活诱导的细胞死亡的抵抗与其不能产生IL-2或产生IL-10的能力无关。这两个群体对Fas诱导的细胞凋亡的敏感性可以通过改变CD 25（+）CD 4（+）：CD 25（-）CD 4（+）T细胞比率在体外调节。CD 25（-）CD 4（+）T细胞对凋亡的敏感性降低，而CD 25（+）CD 4（+）T细胞对凋亡的敏感性增强。Fas依赖性细胞凋亡的调节与细胞因子产生的变化有关。然而，虽然CD 25（-）CD 4（+）T细胞凋亡高度依赖于IL-2（其产生被共培养中的CD 25（+）CD 4（+）T细胞抑制），但CD 25（+）CD 4（+）T细胞凋亡的调节是不依赖于IL-2的。综上所述，这些结果表明，CD 25（+）CD 4（+）和CD 25（-）CD 4（+）T细胞对Fas依赖性凋亡的敏感性在免疫应答期间受到动态调节;这种调节似乎有助于维持调节性T细胞的永久群体：控制效应T细胞所需。
We have previously shown that regulatory CD25(+)CD4(+) T cells are resistant to clonal deletion induced by viral superantigen in vivo. In this work we report that isolated CD25(+)CD4(+) T cells activated in vitro by anti-CD3 Ab are resistant to Fas-induced apoptosis, in contrast to their CD25(-)CD4(+) counterparts. Resistance of CD25(+)CD4(+) T cells to Fas-dependent activation-induced cell death is not linked to their inability to produce IL-2 or to their ability to produce IL-10. The sensitivity of both populations to Fas-induced apoptosis can be modulated in vitro by changing the CD25(+)CD4(+):CD25(-)CD4(+) T cell ratio. The sensitivity of CD25(-)CD4(+) T cells to apoptosis can be reduced, while the sensitivity of CD25(+)CD4(+) T cells can be enhanced. Modulation of Fas-dependent apoptosis is associated with changes in cytokine production. However, while CD25(-)CD4(+) T cell apoptosis is highly dependent on IL-2 (production of which is inhibited by CD25(+)CD4(+) T cells in coculture), modulation of CD25(+)CD4(+) T cell apoptosis is IL-2 independent. Taken together, these results suggest that CD25(+)CD4(+) and CD25(-)CD4(+) T cell sensitivity to Fas-dependent apoptosis is dynamically modulated during immune responses; this modulation appears to help maintain a permanent population of regulatory T cells: required to control effector T cells.