Balancing survival and death of lymphocytes is a vital task of the immune system necessary to maintain its function throughout life. Interleukin-7 (IL-7), produced by stromal cells, plays a key role in promoting proliferation and survival of T cells in periphery. However, the requirements for proliferation and survival for nave and memory T cells appear different. Nave T cells require IL-7 and a weak interaction between TCR and self-peptide/MHC to mediate survival and proliferation while survival and homeostatic proliferation of memory CD4+ T cells can be supported by IL-7 in the absence of TCR signals. Furthermore, memory CD4+ T cells appear to be faster in entering cell cycle than nave CD4+ T cells in response to IL-7 in vitro. 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 nave and memory CD4+ T cells, we observed that more memory CD4+ T cells underwent cell division and proceeded to apoptosis than nave cells in response to IL-7. However, IL-7 induced expressions of Bcl2 family members (Bcl2, Bclxl, Bax and Bad) were similar between nave and memory cells. Instead, we found that IL-7 induced higher levels of telomerase activity in nave 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 TERT 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 nave and memory CD4+ T cells.
| Yang, Yinhua; An, Jie; Weng, Nan-ping (2008) Telomerase is involved in IL-7-mediated differential survival of naive and memory CD4+ T cells. J Immunol 180:3775-81 |
