Welsh R M, Selin L K, Razvi E S
Department of Pathology, University of Massachusetts Medical Center, Worcester 01655, USA.
J Cell Biochem. 1995 Oct;59(2):135-42. doi: 10.1002/jcb.240590202.
Apoptosis is an important mechanism enabling the selection of the non-self-reactive T cell repertoire and for maintaining homeostasis in the immune system after it has expanded to combat infections. Highly activated, proliferating T cells become susceptible to apoptosis driven by a number of stimuli, and T cells activated during a viral infection become susceptible to "activation induced cell death" after repeated stimulation through the T cell receptor (TcR). This is a major mechanism for the immune deficiencies observed during many viral infections. During infections with a high antigen load this can lead to a selective deletion of virus-specific cytotoxic T lymphocytes (CTL) and to the establishment of persistent infection. More commonly, the CTL control the infection first, and high levels of apoptosis in the expanded lymphocyte population occur after antigen and growth factors become limiting. This cell death does not seem to depend on TcR specificity, as the residual population contains a remarkably stable population of memory CTL precursors that approximate the frequency per CD8 cell of that seen during the peak of the acute infection. Subsequent infections with heterologous viruses result in an expansion and then an apoptotic elimination of T cells, with the consequence being a reduction in precursor CTL specific for the first virus. Thus, apoptosis shapes the quality and quantity of T cell memory.
细胞凋亡是一种重要机制，它有助于选择非自身反应性T细胞库，并在免疫系统为对抗感染而扩增后维持其体内平衡。高度活化、增殖的T细胞容易受到多种刺激驱动的细胞凋亡影响，并且在病毒感染期间被激活的T细胞在通过T细胞受体（TcR）反复刺激后会易受“活化诱导的细胞死亡”影响。这是在许多病毒感染期间观察到免疫缺陷的主要机制。在高抗原负荷的感染期间，这可能导致病毒特异性细胞毒性T淋巴细胞（CTL）的选择性缺失，并导致持续性感染的建立。更常见的是，CTL首先控制感染，并且在抗原和生长因子变得有限后，扩增的淋巴细胞群体中会出现高水平的细胞凋亡。这种细胞死亡似乎不依赖于TcR特异性，因为残余群体包含相当稳定的记忆CTL前体细胞群体，其频率接近急性感染高峰期每个CD8细胞所见的频率。随后用异源病毒感染会导致T细胞扩增，然后凋亡消除，结果是针对第一种病毒的前体CTL减少。因此，细胞凋亡塑造了T细胞记忆的质量和数量。
