Regulation of apoptosis in vitro in mature murine spleen T cells.
Regulation of apoptosis in vitro in mature murine spleen T cells.
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DOI：
10.4049/jimmunol.151.7.3521
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发表时间：
1993-10
影响因子：
4.4
通讯作者：
C. Perandones;V. Illera;D. Peckham;L. Stunz;R. Ashman
中科院分区：
文献类型：
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作者：
C. Perandones;V. Illera;D. Peckham;L. Stunz;R. Ashman
先前的研究表明，胸腺细胞在糖皮质激素的作用下会发生细胞凋亡，这是一种程序性细胞死亡的形式。这种经典形式的细胞凋亡是通过抑制蛋白质合成来防止的。本文证实成熟T细胞也会发生凋亡，但脾脏T细胞的凋亡调控与胸腺细胞不同。在没有额外刺激的情况下，成熟的小鼠脾脏T细胞凋亡，而不是坏死。细胞凋亡的检测包括凝胶电泳的核体间DNA切割，二苯胺法的DNA片段率，以及流式细胞术中含有次二倍体DNA的细胞百分比。新鲜脾脏T细胞中凋亡细胞的百分比为2%，至少增加到16 h，凋亡细胞比例为21%。地塞米松引起胸腺和脾脏T细胞凋亡，但在地塞米松诱导的死亡中，只有胸腺细胞需要蛋白质合成。环己亚胺增加脾脏T细胞凋亡，提示细胞凋亡受新合成的保护蛋白控制。与胸腺细胞不同，活化蛋白激酶C可减少脾脏T细胞的自发凋亡，而抑制蛋白激酶的H7和staurosporine可增加脾脏T细胞的自发凋亡。蛋白激酶A/G抑制剂HA1004也能降低脾脏T细胞凋亡。环己亚胺对胸腺细胞和脾脏T细胞的影响在相同的浓度范围内，对PMA也是如此。地塞米松剂量-反应曲线相似，除了更大比例的脾脏T细胞对地塞米松耐药。这些数据支持了一个假设，即T细胞的凋亡程序在其成熟过程中经历了一个转变，因此成熟T细胞的凋亡受到的调节更像成熟B细胞而不是胸腺细胞。
Previously it has been shown that thymocytes undergo apoptosis, a form of programmed cell death, in response to glucocorticoids. This classic form of apoptosis is prevented by inhibition of protein synthesis. The current paper demonstrates that mature T cells also undergo apoptosis, but that the regulation of apoptosis in spleen T cells differs from that of thymocytes. Mature mouse spleen T cells were shown to die by apoptosis, not necrosis, when cultured without an added stimulus. Assays for apoptosis included internucleosomal DNA cleavage by gel electrophoresis, percent fragmentation of DNA by the diphenylamine method, and percent of cells with hypodiploid DNA by flow cytometry. The percent of apoptotic cells was 2% in fresh spleen T cells, and increased at least until 16 h, when 21% were apoptotic. Dexamethasone caused apoptosis in both thymus and spleen T cells, but only thymocytes showed a requirement for protein synthesis in dexamethasone-induced death. Cycloheximide increased apoptosis in spleen T cells, indicating that apoptosis was controlled by newly synthesized protective proteins. Spontaneous apoptosis was decreased in spleen T cells by protein kinase C activation, and was increased by H7 and staurosporine, which inhibits protein kinases, in contrast with the behavior of thymocytes. The protein kinase A/G inhibitor HA1004 also decreased spleen T cell apoptosis. The contrasting effects of cycloheximide on thymocytes and spleen T cells occurred over the same concentration range, and the same was true for PMA. The dexamethasone dose-response curves were similar, except that a greater proportion of spleen T cells were dexamethasone-resistant. These data support the hypothesis that the apoptosis program in T cells undergoes a transition during their maturation, such that apoptosis in mature T cells is regulated more like that of mature B cells than that of thymocytes.