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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Proliferating γδ T cells manifest high and spatially confined caspase-3 activity
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Proliferating γδ T cells manifest high and spatially confined caspase-3 activity

机译：增殖的γδT细胞表现出高水平和空间受限的caspase-3活性

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摘要

Caspase-8 serves two paradoxical roles in T lymphocytes: it initiates apoptosis following death receptor engagement, and is also indispensible for proliferation following T-cell antigen receptor (TCR) signalling. These opposing processes appear to be controlled by both spatial and quantitative differences in caspase-8 activation. Given differences in the turnover of T-cell subsets, we compared caspase activity and susceptibility to cell death following TCR restimulation in murine CD4 + and CD8 +αβ T cells and γδ T cells. We observed a spectrum of caspase activity in non-dying effector T cells in which CD4 + T cells manifested the lowest levels of active caspases whereas γδ T cells manifested the highest levels. Further analysis revealed that most of the difference in T-cell subsets was the result of high levels of active caspase-3 in non-dying effector γδ T cells. Despite this, γδ T cells manifested little spontaneous or CD3 restimulation-induced cell death as the result of confinement of active caspases to the cell membrane. By contrast, CD4 + T cells were highly sensitive to CD3-induced cell death, associated with the appearance of active caspases in the cytoplasm and cleavage of the caspase substrates Bid and ICAD. Hence, the location and amount of active caspases distinguishes effector T-cell subsets and profoundly influences the fate of the T-cell response.
机译：Caspase-8在T淋巴细胞中具有两个矛盾的作用：它在死亡受体参与后启动凋亡，并且在T细胞抗原受体（TCR）信号转导后也是不可缺少的。这些相反的过程似乎受caspase-8激活的空间和数量差异的控制。鉴于T细胞亚群的营业额差异，我们比较了鼠CD4 +和CD8 +αβT细胞和γδT细胞中TCR再刺激后caspase的活性和对细胞死亡的敏感性。我们观察到非垂死的效应T细胞中的半胱天冬酶活性谱，其中CD4 + T细胞表现出最低水平的活性胱天蛋白酶，而γδT细胞表现出最高水平。进一步的分析表明，T细胞亚群的大部分差异是由于非死亡效应子δδT细胞中高水平的活性caspase-3所致。尽管如此，由于活性胱天蛋白酶限制在细胞膜上，γδT细胞几乎没有表现出自发性或CD3再刺激诱导的细胞死亡。相比之下，CD4 + T细胞对CD3诱导的细胞死亡高度敏感，这与细胞质中活跃的胱天蛋白酶的出现以及胱天蛋白酶底物Bid和ICAD的裂解有关。因此，活性胱天蛋白酶的位置和数量区分了效应T细胞亚群，并深刻影响了T细胞应答的命运。

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