Wellcome Trust Immunology Unit, University of Cambridge, Cambridge, United Kingdom.
J Immunol. 2010 Dec 15;185(12):7141-5. doi: 10.4049/jimmunol.1002537. Epub 2010 Nov 10.
Persistent viral infections induce the differentiation and accumulation of large numbers of senescent CD8(+) T cells, raising the possibility that repetitive stimulation drives clones of T cells to senesce. It is therefore unclear whether T cell responses are maintained by the self-renewal of Ag-experienced peripheral T cell subsets or by the continuous recruitment of newly generated naive T cells during chronic infections. Using a transgenic mouse model that permits the indelible marking of granzyme B-expressing cells, we found that T cells primed during the initial stages of a persistent murine γ-herpes infection persisted and continued to divide during a latent phase of up to 7 mo. Such cells maintained an ability to extensively replicate in response to challenge with influenza virus expressing the same Ag. Therefore, Ag-experienced, virus-specific CD8(+) T cell populations contain a subset that maintains replicative potential, despite long-term, persistent antigenic stimulation.
持续性病毒感染诱导大量衰老的 CD8(+)T 细胞的分化和积累，这使得重复刺激可能导致 T 细胞克隆衰老。因此，尚不清楚 T 细胞反应是通过抗原经验外周 T 细胞亚群的自我更新来维持，还是在慢性感染期间通过不断招募新产生的幼稚 T 细胞来维持。使用一种转基因小鼠模型，该模型允许不可磨灭地标记表达颗粒酶 B 的细胞，我们发现，在持续性小鼠 γ-疱疹病毒感染的初始阶段被引发的 T 细胞在长达 7 个月的潜伏期内持续存在并继续分裂。这些细胞在受到表达相同抗原的流感病毒的挑战时，仍然能够广泛复制。因此，尽管存在长期持续性抗原刺激，抗原经验丰富的、病毒特异性的 CD8(+)T 细胞群体中包含一个亚群，该亚群保持着复制潜能。
