Interplay between cell division and cell death during TCR triggering
Interplay between cell division and cell death during TCR triggering
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DOI：
10.1002/eji.200425271
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发表时间：
2004-09-01
影响因子：
5.4
通讯作者：
Combadiere, B
中科院分区：
文献类型：
--
作者：
Boissonnas, A;Combadiere, B
细胞死亡是避免T细胞过度扩增的关键。在原代T细胞响应病原体扩增或接种后，外源Ag的数量决定了克隆扩增和死亡的程度。在这里，我们研究了在TCR触发过程中细胞增殖和死亡之间的平衡，以及细胞死亡的易感性。用高剂量的鸽子细胞色素c肽88-104诱导AND-TCR （Vbeta3, Vaalpha11）转基因小鼠CD4 T细胞后，与低剂量的Ag相比，细胞扩增率明显降低，克隆消除明显，而在所有Ag剂量下达到的细胞分裂数相似。TCR再次作用于活化的T细胞诱导细胞死亡，与初次刺激时遇到的银剂量无关。令人惊讶的是，在体外和体内，所有分裂细胞早在第一次分裂时就发生了凋亡。这种现象具有高度选择性，因为激活但未分裂的细胞不会发生细胞死亡，而曾经分裂过的细胞则容易发生细胞死亡。这些发现对银激发后的外周稳态机制和设计初级/加强疫苗策略具有直接意义。
Cell death is crucial to avoid excessive T cell expansion. During primary T cell expansion in response to pathogen or after vaccination, the amount of foreign Ag determines the degree of clonal amplification and death. Here, we studied the balance between cell proliferation and death, as well as susceptibility to cell death, during TCR triggering. After priming of CD4 T cells from AND-TCR (Vbeta3, Vaalpha11)-transgenic mice with a high dose of pigeon cytochrome c peptide 88-104, the cell expansion rate was significantly reduced by marked clonal elimination compared to lower Ag doses, whereas the number of cell divisions reached was similar at all Ag doses. TCR re-engagement on activated T cells induced cell death, irrespective of the dose of Ag encountered during primary stimulation. Surprisingly, commitment to apoptosis occurred as early as the first division on all dividing cells both in vitro and in vivo. This phenomenon was highly selective, as activated but non-dividing cells did not undergo cell death, whereas cells that had divided once became susceptible to cell death. These findings have direct implications for the peripheral homeostatic mechanism following Ag challenge and for designing primary/booster vaccine strategies.