In vitro generated human memory-like T cells are CD95 type II cells and resistant towards CD95-mediated apoptosis
In vitro generated human memory-like T cells are CD95 type II cells and resistant towards CD95-mediated apoptosis
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DOI：
10.1002/eji.200635925
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发表时间：
2006-11-01
影响因子：
5.4
通讯作者：
Krammer, Peter H.
中科院分区：
文献类型：
--
作者：
Fas, Stefanie C.;Baumann, Sven;Krammer, Peter H.
适应性免疫反应意味着激活的T细胞的扩张和随后的消除，以在被称为激活诱导细胞死亡的过程中维持内稳态。然而，一些细胞会分化为记忆细胞，并确保产生强大的二次免疫反应。为了从细胞和分子水平分析记忆T细胞的凋亡表型，我们建立了一个与记忆细胞表型和功能相似的T细胞激活和细胞生成的体外模型。这些长期培养的T细胞表现出CD95抗性的表型，尽管它们对TCR/CD3介导的凋亡仍然敏感。生化分析显示，这些细胞在效应期从CD95 I型(来自受体的直接信号)转变为CD95 II型细胞(依赖于线粒体扩增环)。此外，他们的线粒体受到保护，可能是由于高水平的Bclx(L)和Bcl2的表达。因此，我们的数据提示了记忆T细胞如何通过CD95系统获得对旁观者细胞死亡的抵抗的机制。
An adaptive immune response implies expansion of activated T cells and subsequent elimination to maintain homeostasis in a process called activation-induced cell death. Some cells, however, differentiate into memory cells and ensure a strong secondary immune response. To analyze the apoptosis phenotype of memory T cells on a cellular and molecular level, we have established an in vitro model of T cell activation and generation of cells phenotypically and functionally similar to memory cells. These long-term cultured T cells show a CD95-resistant phenotype, although they are still sensitive towards TCR/CD3-mediated apoptosis. Biochemical analysis revealed that these cells shift from CD95 type I (direct signaling from the receptor) during the effector phase to CD95 type II cells (dependent on the mitochondrial amplification loop). Moreover, their mitochondria are protected, probably due to high expression levels of Bcl-x(L) and Bcl-2. Thus, our data suggest a mechanism how memory T cells acquire resistance towards bystander cell death via the CD95 system.