Yang Yinhua, An Jie, Weng Nan-ping
Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
J Immunol. 2008 Mar 15;180(6):3775-81. doi: 10.4049/jimmunol.180.6.3775.
IL-7 plays an essential role in T cell maintenance and survival. The survival effect of IL-7 is thought to be mediated through regulation of Bcl2 family proteins. After a comparative analysis of IL-7-induced growth and cell death of human naive and memory CD4(+) T cells, we observed that more memory CD4(+) T cells underwent cell division and proceeded to apoptosis than naive cells in response to IL-7. However, IL-7-induced expressions of Bcl2 family members (Bcl2, Bcl-x(L), Bax, and Bad) were similar between naive and memory cells. Instead, we found that IL-7 induced higher levels of telomerase activity in naive cells than in memory cells, and the levels of IL-7-induced telomerase activity had a significant inverse correlation with cell death in CD4(+) T cells. Furthermore, we showed that reducing expression of telomerase reverse transcriptase and telomerase activity significantly increased cell death of IL-7-cultured CD4(+) T cells. Together, these findings demonstrate that telomerase is involved in IL-7-mediated differential survival of naive and memory CD4(+) T cells.
白细胞介素-7（IL-7）在T细胞维持和存活中起关键作用。IL-7的存活效应被认为是通过调节Bcl2家族蛋白介导的。在对IL-7诱导的人类初始和记忆性CD4(+) T细胞生长及细胞死亡进行比较分析后，我们观察到，与初始细胞相比，更多的记忆性CD4(+) T细胞在响应IL-7时经历细胞分裂并进而发生凋亡。然而，IL-7诱导的Bcl2家族成员（Bcl2、Bcl-x(L)、Bax和Bad）表达在初始细胞和记忆细胞之间相似。相反，我们发现IL-7在初始细胞中诱导的端粒酶活性水平高于记忆细胞，且IL-7诱导的端粒酶活性水平与CD4(+) T细胞中的细胞死亡呈显著负相关。此外，我们表明降低端粒酶逆转录酶的表达和端粒酶活性显著增加了IL-7培养的CD4(+) T细胞的细胞死亡。总之，这些发现表明端粒酶参与了IL-7介导的初始和记忆性CD4(+) T细胞的差异性存活。
