Min-Oo Gundula, Bezman Natalie A, Madera Sharline, Sun Joseph C, Lanier Lewis L
Department of Microbiology and Immunology and Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94143.
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065.
J Exp Med. 2014 Jun 30;211(7):1289-96. doi: 10.1084/jem.20132459. Epub 2014 Jun 23.
Apoptosis is critical for the elimination of activated lymphocytes after viral infection. Proapoptotic factor Bim (Bcl2l11) controls T lymphocyte contraction and the formation of memory T cells after infection. Natural killer (NK) cells also undergo antigen-driven expansion to become long-lived memory cells after mouse cytomegalovirus (MCMV) infection; therefore, we examined the role of Bim in regulating the MCMV-driven memory NK cell pool. Despite responding similarly early after infection, Bcl2l11(-/-) Ly49H(+) NK cells show impaired contraction and significantly outnumber wild-type (WT) cells after the expansion phase. The inability to reduce the effector pool leads to a larger Bcl2l11(-/-) NK memory subset, which displays a less mature phenotype (CD11b(lo), CD27(+)) and lower levels of NK cell memory-associated markers KLRG1 and Ly6C. Bcl2l11(-/-) memory NK cells demonstrate a reduced response to m157-mediated stimulation and do not protect as effectively as WT memory NK cells in an MCMV challenge model. Thus, Bim-mediated apoptosis drives selective contraction of effector NK cells to generate a pool of mature, MCMV-specific memory cells.
凋亡对于病毒感染后活化淋巴细胞的清除至关重要。促凋亡因子Bim（Bcl2l11）控制感染后T淋巴细胞的收缩以及记忆性T细胞的形成。自然杀伤（NK）细胞在小鼠巨细胞病毒（MCMV）感染后也会经历抗原驱动的扩增，从而成为长寿的记忆细胞；因此，我们研究了Bim在调节MCMV驱动的记忆性NK细胞库中的作用。尽管在感染后早期反应相似，但Bcl2l11（-/-）Ly49H（+）NK细胞的收缩受损，并且在扩增阶段后数量明显超过野生型（WT）细胞。无法减少效应细胞库导致更大的Bcl2l11（-/-）NK记忆亚群，其表现出不太成熟的表型（CD11b（lo），CD27（+））以及较低水平的NK细胞记忆相关标志物KLRG1和Ly6C。Bcl2l11（-/-）记忆性NK细胞对m157介导的刺激反应减弱，并且在MCMV攻击模型中不像WT记忆性NK细胞那样有效地发挥保护作用。因此，Bim介导的凋亡驱动效应性NK细胞的选择性收缩，以产生一群成熟的、MCMV特异性的记忆细胞。
