A1 is a growth-permissive antiapoptotic factor mediating postactivation survival in T cells
A1 is a growth-permissive antiapoptotic factor mediating postactivation survival in T cells
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DOI：
10.1182/blood-2002-04-1229
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发表时间：
2003-04-01
期刊：
影响因子：
20.3
通讯作者：
Prystowsky, MB
中科院分区：
文献类型：
--
作者：
Gonzalez, J;Orlofsky, A;Prystowsky, MB
活化的初始T细胞中细胞死亡的调节还没有很好地理解。我们研究了A1的表达，Bcl-2家族的抗凋亡成员，幼稚小鼠脾细胞激活后。A1基因的表达强烈，但短暂诱导在第一天的激活，在2至6小时的峰值，而Bcl-2 mRNA同时瞬时下调。通过lck远端启动子在T细胞中A1-a的转基因（Tg）过表达导致在用伴刀豆球蛋白A或用针对CD 3和CD 28的抗体激活后细胞凋亡减少，并导致T细胞产量在5天内加倍。Tg A1-a也部分保护胸腺细胞免受几种促凋亡刺激，但不能保护T细胞母细胞免受通过T细胞受体再激活诱导的细胞死亡。Tg Bcl-2和Tg A1-a在静息和活化的T细胞中都显示出类似的减少凋亡的能力。然而，在活化的脾细胞培养物中，用Tg Bcl-2观察到的5天T细胞产量的增加仅为Tg A1-a产生的增加的一半。这种差异可能至少部分归因于A1不像Bcl-2那样抑制活化细胞进入S期。A1蛋白可能代表Bcl-2基因家族在增殖刺激的背景下对生存调节的需要的适应。
The regulation of cell death in activated naive T cells is not well understood. We examined the expression of A1, an antiapoptotic member of the Bcl-2 family, following activation of naive mouse splenocytes. A1 gene expression was strongly but transiently induced during the first day of activation, with a peak at 2 to 6 hours, whereas Bcl-2 mRNA was simultaneously transiently down-regulated. Transgenic (Tg) overexpression of A1-a in T cells via the lck distal promoter resulted in decreased apoptosis following activation either with concanavalin A or with antibodies to CD3 and CD28 and led to a doubling of T-cell yield by 5 days. Tg A1-a also partially protected thymocytes from several proapoptotic stimuli but did not protect T-cell blasts from cell death induced by reactivation via the T-cell receptor. Tg Bcl-2 and Tg A1-a showed a similar ability to reduce apoptosis in both resting and activated T cells. However, in activated splenocyte cultures, the increase in 5-day T-cell yield observed with Tg Bcl-2 was only half that produced by Tg A1-a. This difference could be attributed at least in part to the fact that A1, unlike Bcl-2, did not inhibit S-phase entry of activated cells. The A1 protein may represent an adaptation of the Bcl-2 gene family to the need for survival regulation in the context of a proliferative stimulus.