Maraskovsky E, O'Reilly L A, Teepe M, Corcoran L M, Peschon J J, Strasser A
Department of Cellular Immunology, Immunex Research and Development Corporation, Seattle, Washington 98101, USA.
Cell. 1997 Jun 27;89(7):1011-9. doi: 10.1016/s0092-8674(00)80289-5.
Signals from cytokine and antigen receptors play crucial roles during lymphocyte development. Mice lacking interleukin-7 receptor are lymphopenic, due to a defect in cell expansion at an early stage of differentiation, and the few mature T cells that develop in IL-7R-/- animals are functionally impaired. Both defects were rescued completely by overexpression of the anti-apoptosis protein Bcl-2. T cell progenitors lacking antigen receptor molecules are also blocked in differentiation and die, presumably because they fail to receive a positive signal via their pre-T cell receptor. Surprisingly, Bcl-2 did not promote survival or differentiation of T cells in rag-1-/- mice. These results provide evidence that blocking apoptosis is the essential function of IL-7R during differentiation and activation of T lymphocytes and that pre-TCR signaling blocks a pathway to apoptosis that is insensitive to Bcl-2.
细胞因子和抗原受体发出的信号在淋巴细胞发育过程中发挥着关键作用。缺乏白细胞介素-7受体的小鼠出现淋巴细胞减少，这是由于在分化早期细胞扩增存在缺陷，并且在IL-7R-/-动物中发育的少数成熟T细胞功能受损。通过抗凋亡蛋白Bcl-2的过表达，这两个缺陷都得到了完全挽救。缺乏抗原受体分子的T细胞祖细胞在分化过程中也会受阻并死亡，推测是因为它们无法通过前T细胞受体接收阳性信号。令人惊讶的是，Bcl-2并未促进rag-1-/-小鼠中T细胞的存活或分化。这些结果证明，在T淋巴细胞的分化和激活过程中，阻断凋亡是IL-7R的基本功能，并且前TCR信号传导阻断了一条对Bcl-2不敏感的凋亡途径。
