Whitmire Jason K, Eam Boreth, Whitton J Lindsay
Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, California, United States of America.
PLoS Pathog. 2008 Apr 11;4(4):e1000041. doi: 10.1371/journal.ppat.1000041.
T cell memory is a cornerstone of protective immunity, and is the key element in successful vaccination. Upon encountering the relevant pathogen, memory T cells are thought to initiate cell division much more rapidly than their naïve counterparts, and this is thought to confer a significant biological advantage upon an immune host. Here, we use traceable TCR-transgenic T cells to evaluate this proposed characteristic in CD4+ and CD8+ memory T cells. We find that, even in the presence of abundant antigen that was sufficient to induce in vivo IFNgamma production by memory T cells, both memory and naïve T cells show an extended, and indistinguishable, delay in the onset of proliferation. Although memory cells can detect, and respond to, virus infection within a few hours, their proliferation did not begin until approximately 3 days after infection, and occurred simultaneously in all anatomical compartments. Thereafter, cell division was extraordinarily rapid for both naïve and memory cells, with the latter showing a somewhat accelerated accumulation. We propose that, by permitting memory T cells to rapidly exert their effector functions while delaying the onset of their proliferation, evolution has provided a safeguard that balances the risk of infection against the consequences of severe T cell-mediated immunopathology.
T细胞记忆是保护性免疫的基石，也是成功接种疫苗的关键要素。在遇到相关病原体时，记忆T细胞被认为比其初始对应细胞启动细胞分裂的速度要快得多，这被认为赋予了免疫宿主显著的生物学优势。在此，我们使用可追踪的TCR转基因T细胞来评估CD4+和CD8+记忆T细胞中的这一特性。我们发现，即使存在足以诱导记忆T细胞在体内产生IFNγ的丰富抗原，记忆T细胞和初始T细胞在增殖开始时都表现出延长且难以区分的延迟。尽管记忆细胞能在数小时内检测并对病毒感染做出反应，但其增殖直到感染后约3天才开始，且在所有解剖部位同时发生。此后，初始T细胞和记忆细胞的细胞分裂都异常迅速，后者的积累略有加速。我们提出，通过允许记忆T细胞在延迟其增殖开始的同时迅速发挥其效应功能，进化提供了一种保障，平衡了感染风险与严重T细胞介导的免疫病理后果。
