Cell-Intrinsic Defects in the Proliferative Response of Antiviral Memory CD8 T Cells in Aged Mice upon Secondary Infection
Cell-Intrinsic Defects in the Proliferative Response of Antiviral Memory CD8 T Cells in Aged Mice upon Secondary Infection
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DOI：
10.4049/jimmunol.0902063
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发表时间：
2010-05-01
影响因子：
4.4
通讯作者：
Wherry, E. John
中科院分区：
文献类型：
--
作者：
Decman, Vilma;Laidlaw, Brian J.;Wherry, E. John
尽管先前的研究已经证明了在感染期间老年小鼠中延迟的病毒清除和钝化的效应T细胞应答，但记忆性CD 8 T细胞特别是继发性应答受到的关注较少。在这项研究中，我们发现，在老年与年轻动物中形成的记忆性CD 8 T细胞数量的适度差异与记忆性CD 8 T细胞分化的改变有关。老年免疫小鼠在二次病毒攻击后发病率和死亡率增加，表明T细胞免疫力发生变化。事实上，来自老年小鼠的病毒特异性记忆CD 8 T细胞在使用多种攻击模型的继发感染后显示出显著降低的增殖扩增。此外，老年记忆CD 8 T细胞的回忆能力缺陷是细胞内在的，并且在过继转移到年轻小鼠中后持续存在。因此，记忆T细胞的增殖潜力差和改变的记忆CD 8 T细胞分化可能是抗病毒免疫中年龄相关缺陷的基础。免疫学杂志，2010，184：5151-5159。
Although previous studies have demonstrated delayed viral clearance and blunted effector T cell responses in aged mice during infection, memory CD8 T cells and especially secondary responses have received less attention. In this study, we show that modest differences in the number of memory CD8 T cells formed in aged versus young animals were associated with altered memory CD8 T cell differentiation. Aged immune mice had increased morbidity and mortality upon secondary viral challenge, suggesting changes in T cell immunity. Indeed, virus-specific memory CD8 T cells from aged mice showed substantially reduced proliferative expansion upon secondary infection using multiple challenge models. In addition, this defect in recall capacity of aged memory CD8 T cells was cell-intrinsic and persisted upon adoptive transfer into young mice. Thus, the poor proliferative potential of memory T cells and altered memory CD8 T cell differentiation could underlie age-related defects in antiviral immunity. The Journal of Immunology, 2010, 184: 5151-5159.