Antigen-specific CD8+ T cell clonal expansions develop from memory T cell pools established by acute respiratory virus infections
Antigen-specific CD8+ T cell clonal expansions develop from memory T cell pools established by acute respiratory virus infections
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DOI：
10.4049/jimmunol.179.6.3535
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发表时间：
2007-09-15
影响因子：
4.4
通讯作者：
Woodland, David L.
中科院分区：
文献类型：
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作者：
Ely, Kenneth H.;Ahmed, Mushtaq;Woodland, David L.
年龄的增长与CD8(+) T细胞克隆扩增（TCE）的发展有关，TCE可以支配外周T细胞库并干扰对感染和疫苗接种的免疫反应。一些TCE是由慢性感染驱动的，与T细胞克隆在持续抗原刺激下生长失调一致。然而，第二类TCE在没有慢性感染的情况下随着年龄的增长而发展，并且在起源或Ag依赖性方面知之甚少。在这项研究中，我们提出证据表明，非持续性流感和副流感病毒感染引发的传统记忆CD8(+) T细胞池以高频率发生ag特异性TCE。推测的TCE发生在中枢记忆和效应记忆CD8(+) T细胞群中，并且不需要Ag来维持。此外，它们在表型和功能上与正常记忆T细胞相似，表明它们是从记忆T细胞池中随机发育而来的。这些数据表明，记忆T细胞池随着时间的推移逐渐失调，这可能对老年人的免疫反应产生重大影响。
Increasing age is associated with the development of CD8(+) T cell clonal expansions (TCE) that can dominate the peripheral T cell repertoire and interfere with immune responses to infection and vaccination. Some TCE are driven by chronic infections, consistent with dysregulated outgrowth of T cell clones in response to persistent antigenic stimulation. However, a second class of TCE develops with age in the absence of chronic infections and is poorly understood in terms of origin or Ag dependence. In this study, we present evidence that Ag-specific TCE develop at high frequencies from conventional memory CD8(+) T cell pools elicited by nonpersistent influenza and parainfluenza virus infections. Putative TCE occurred in both the central- and effector-memory CD8(+) T cell populations and did not require Ag for their maintenance. In addition, they were similar to normal memory T cells in terms of phenotype and function, suggesting that they develop stochastically from the memory T cell pool. These data suggest that memory T cell pools become progressively dysregulated over time and this may have a significant impact on immune responsiveness in the aged.