Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Cell Immunol. 2011;271(2):256-66. doi: 10.1016/j.cellimm.2011.07.003. Epub 2011 Jul 24.
During many infections, large numbers of effector CD8(+) T cells are generated. After pathogen clearance, the majority of these cells undergo apoptosis, while the survivors differentiate into memory CD8(+) T cells. Although loss of both Bim and Fas function dramatically increased antigen-specific CD8(+) T cells in the lymph nodes following acute lymphocytic choriomeningitis virus (LCMV) infection, it was unclear whether they were pardoned effector or true memory CD8(+) T cells. In this study, we demonstrate they are bona fide memory T cells as characterized by surface marker expression, cytokine production, homeostatic proliferation, and ability to clear a secondary challenge of pathogen. Loss of both Bim and Fas also increased the number of virus-specific CD4(+) T cells found in the lymph nodes compared to the parental genotypes or wildtype mice. These studies illustrate that decreasing apoptosis increases the number of memory T cells and therefore could increase the efficacy of vaccines.
在许多感染中,会产生大量的效应性 CD8(+) T 细胞。病原体清除后,这些细胞中的大多数会发生凋亡,而存活下来的细胞则分化为记忆性 CD8(+) T 细胞。尽管 Bim 和 Fas 功能缺失都显著增加了急性淋巴细胞脉络丛脑膜炎病毒 (LCMV) 感染后淋巴结中抗原特异性 CD8(+) T 细胞的数量,但尚不清楚它们是被赦免的效应细胞还是真正的记忆性 CD8(+) T 细胞。在这项研究中,我们通过表面标志物表达、细胞因子产生、稳态增殖和清除病原体二次挑战的能力证明它们是真正的记忆 T 细胞。与亲本基因型或野生型小鼠相比,Bim 和 Fas 双缺失也增加了淋巴结中病毒特异性 CD4(+) T 细胞的数量。这些研究表明,减少细胞凋亡会增加记忆 T 细胞的数量,从而提高疫苗的疗效。