Karrer Urs, Sierro Sophie, Wagner Markus, Oxenius Annette, Hengel Hartmut, Koszinowski Ulrich H, Phillips Rodney E, Klenerman Paul
Nuffield Department of Clinical Medicine, University of Oxford, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UK.
J Immunol. 2003 Feb 15;170(4):2022-9. doi: 10.4049/jimmunol.170.4.2022.
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 MCMV-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.
CD8 + T淋巴细胞在急性和持续性感染期间对细胞内病原体的控制中发挥着重要作用。对于持续性疱疹病毒，如人类巨细胞病毒（CMV）而言尤其如此，在病毒潜伏期间，这类病毒以大量病毒特异性CD8 + T细胞群体为特征。为了了解这些细胞群体的起源以及随着时间推移塑造它们的因素，我们研究了小鼠巨细胞病毒（MCMV）感染后的CD8 + T细胞反应。急性反应的动力学特征是活化T细胞迅速扩增，随后是一个收缩期。此后，我们观察到一种显著的模式，即MCMV特异性记忆CD8 + T细胞随时间稳步积累，在1年时所有CD8 + T细胞中有20%对一个MCMV表位具有特异性。在所有测试器官中均可见MCMV特异性CD8 + T淋巴细胞的积累，并且与特异性CD8 + T淋巴细胞的持续活化相关，主要发生在淋巴结内。在测试的五个表位中，仅在其中两个表位中观察到积累模式，并且随着时间的推移，TCRβ链可变区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，持续或反复接触抗原可以缓慢塑造记忆T细胞群体。这可能与理解人类中所见的大量人类CMV特异性CD8 + T细胞群体的演变有关。
