Wherry E John, Becker Todd C, Boone David, Kaja Murali-Krishna, Ma Averil, Ahmed Rafi
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Adv Exp Med Biol. 2002;512:165-75. doi: 10.1007/978-1-4615-0757-4_22.
The generation and efficient maintenance of antigen specific memory T cells is essential for long-lasting immunological protection. Antigen specific memory CD8 T cells are known to be maintained via antigen-independent homeostatic proliferation. However, signals that drive memory T cell generation and/or influence the slow turnover of memory T cells are unknown. Recently, IL-15 has received attention for its potential effect on memory CD8 T cells. In this report we examine the role of IL-15 in the generation and maintenance of virus specific memory CD8 T cells using mice deficient in either IL-15 or the IL-15 receptor a chain. Both cytokine and receptor deficient mice mount a robust CD8 T cell response to infection with lymphocytic choriomeningitis virus (LCMV) that is initially only slightly lower than in control mice. Further, virus specific memory CD8 T cells are generated in both IL-15 -/- and IL-15Ralpha -/- mice. However, longitudinal analysis reveals a slow attrition of LCMV specific memory CD8 T cells in the absence of IL-15 signals. Indeed, direct examination of homeostatic proliferation reveals a severe defect in the turnover of antigen specific memory CD8 T cells in the absence of IL-15. Together these results suggest that IL-15 is not essential for the generation of memory CD8 T cells, but is required for homeostatic proliferation to maintain populations of memory cells over long periods of time.
抗原特异性记忆T细胞的产生和有效维持对于持久的免疫保护至关重要。已知抗原特异性记忆CD8 T细胞通过抗原非依赖性稳态增殖得以维持。然而，驱动记忆T细胞产生和/或影响记忆T细胞缓慢更新的信号尚不清楚。最近，白细胞介素-15（IL-15）因其对记忆CD8 T细胞的潜在作用而受到关注。在本报告中，我们使用IL-15或IL-15受体α链缺陷的小鼠，研究了IL-15在病毒特异性记忆CD8 T细胞产生和维持中的作用。细胞因子和受体缺陷小鼠对淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染均产生强烈的CD8 T细胞应答，最初仅略低于对照小鼠。此外，在IL-15 -/-和IL-15Rα -/-小鼠中均产生了病毒特异性记忆CD8 T细胞。然而，纵向分析显示，在缺乏IL-15信号的情况下，LCMV特异性记忆CD8 T细胞会缓慢减少。事实上，对稳态增殖的直接检测表明，在缺乏IL-15的情况下，抗原特异性记忆CD8 T细胞的更新存在严重缺陷。这些结果共同表明，IL-15对于记忆CD8 T细胞的产生并非必不可少，但对于稳态增殖以长期维持记忆细胞群体是必需的。
