Memory inflation:: Continuous accumulation of antiviral CD8+ T cells over time

Memory inflation:: Continuous accumulation of antiviral CD8+ T cells over time
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DOI:
10.4049/jimmunol.170.4.2022
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发表时间:
2003-02-15
影响因子:
4.4
通讯作者:
Klenerman, P
Klenerman, P
中科院分区:
医学2区
文献类型:
--
作者:
Karrer, U;Sierro, S;Klenerman, P

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被引文献

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CD8(+) T淋巴细胞在急性和持续性感染期间的细胞内病原体控制中发挥重要作用。在持久性疱疹病毒(如人类巨细胞病毒)的情况下尤其如此,在病毒潜伏期间,其典型特征是大量病毒特异性CD8(+) T细胞群。为了了解这些群体的起源以及随着时间的推移形成它们的因素,我们研究了小鼠CMV (MCMV)感染后CD8(+) T细胞的反应。急性反应的动力学特征是激活T细胞的快速扩张,随后是收缩期。此后,我们观察到一个惊人的模式,MCMV特异性记忆CD8(+) T细胞随着时间的推移稳步积累,所有CD8(+) T细胞中有20%对一个MCMV表位具有1年特异性。mcniv特异性CD8(+) T淋巴细胞的积累在所有测试器官中都可见,并且与特异性CD8(+) T淋巴细胞的持续激活有关,主要是在淋巴结内。累积模式仅在测试的五个表位中的两个中观察到,并且随着时间的推移,TCR β链可变区域的使用逐渐受到限制。这种病毒特异性CD8(+) T细胞反应的新模式表明,随着时间的推移,连续或重复暴露于Ag可以缓慢地塑造记忆T细胞群。这可能与理解人类cmv特异性CD8(+) T细胞群的进化有关。中华免疫学杂志,2003,17(2):522 - 529。
CD8(+) T lymphocytes play an important role in the control of intracellular pathogens during both acute and persistent infections. This is particularly true in the case of persistent herpesviruses such as human CMV, which are typified by large virus-specific CD8(+) T cell populations during viral latency. To understand the origin of, these populations and the factors shaping them over time, we investigated the CD8(+) T cell response after murine CMV (MCMV) infection. The kinetics of the acute response were characterized by rapid expansion of activated T cells, followed by a contraction phase. Thereafter, we observed a striking pattern, where MCMV-specific memory CD8(+) T cells steadily accumulated over time, with 20% of all CD8(+) T cells at 1 year specific for one MCMV epitope. Accumulation of MCNIV-specific CD8(+) T lymphocytes was seen in all organs tested and was associated with continuous activation of specific CD8(+) T lymphocytes, primarily within lymph nodes. The pattern of accumulation was observed in only two of five epitopes tested, and was accompanied by a gradual restriction in usage of the variable region of the TCR beta-chain over time. This novel pattern of a virus-specific CD8(+) T cell response suggests that continuous or repetitive exposure to Ag can slowly mold memory T cell populations over time. This may be relevant for understanding the evolution of the large human CMV-specific CD8(+) T cell populations seen in humans. The Journal of Immunology, 2003, 170: 2022-2029.