Circulating herpes simplex type 1 (HSV-1)-specific CD8+ T cells do not access HSV-1 latently infected trigeminal ganglia.
Circulating herpes simplex type 1 (HSV-1)-specific CD8+ T cells do not access HSV-1 latently infected trigeminal ganglia.
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DOI：
10.1186/2042-4280-2-5
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发表时间：
2011-03-15
期刊：
影响因子：
--
通讯作者：
Hendricks RL
中科院分区：
文献类型：
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作者：
Himmelein S;St Leger AJ;Knickelbein JE;Rowe A;Freeman ML;Hendricks RL
治疗性疫苗可以被设计为增强现有的T细胞记忆群体，以增加对再感染的保护。在单纯疱疹病毒1型的情况下，复发性疾病是由感觉神经节中潜伏病毒的再活化引起的，其部分地由神经节驻留的HSV特异性记忆CD 8 + T细胞群控制。因此，治疗性HSV-1疫苗的一个重要目标将是增强该群体。在急性和潜伏感染期间，用TAK-779处理HSV-1感染小鼠，以阻断CCR 5和CXCR 3介导的CD 8 + T细胞迁移。此外，将HSV-1特异性CD 8 + T细胞转移到HSV-1潜伏感染的小鼠中以模拟治疗性疫苗的作用，并在稳态潜伏期期间或在应激和皮质酮诱导的耗竭和HSV-1从潜伏期再激活后TG驻留记忆CD 8 + T细胞群的恢复期间追踪它们向三叉神经节（TG）的迁移。溴脱氧尿苷（BrdU）掺入测量体内细胞增殖。急性HSV-1感染期间TAK-779治疗减少了浸润性CD 8 + T细胞的数量，但未改变病毒基因组拷贝数。HSV潜伏期期间的TAK-779给药不影响TG驻留记忆CD 8 + T细胞群的大小。转移的HSV特异性CD 8 + T细胞在稳态潜伏期期间或在潜伏感染小鼠暴露于应激和皮质酮后TG驻留的HSV特异性CD 8 + T细胞群体的恢复期间未能接近潜伏感染的TG。在应激和皮质酮治疗后，HSV特异性CD 8 + T细胞群体的恢复发生在细胞分裂的稳态水平，并且不需要CD 4 + T细胞的帮助。我们的研究结果与以下观点一致，即潜伏感染的TG中的CD 8 + T细胞是组织驻留记忆（Trm）群体，其在没有来自外周的补充的情况下维持，并且当该群体被破坏时，其恢复而没有增殖或从血液中可检测到的HSV特异性CD 8 + T细胞的募集。潜伏感染的TG中HSV特异性CD 8+记忆T细胞群的区室化将使治疗性疫苗的设计复杂化。
Therapeutic vaccines can be designed to enhance existing T cell memory populations for increased protection against re-infection. In the case of herpes simplex virus type 1, recurrent disease results from reactivation of latent virus in sensory ganglia, which is controlled in part by a ganglia-resident HSV-specific memory CD8+ T cell population. Thus, an important goal of a therapeutic HSV-1 vaccine would be to enhance this population. HSV-1-infected mice were treated with TAK-779 to block CCR5- and CXCR3-mediated CD8+ T cell migration during both acute and latent infections. Additionally, HSV-1-specific CD8+ T cells were transferred into HSV-1 latently infected mice to mimic the effect of a therapeutic vaccine, and their migration into trigeminal ganglia (TG) was traced during steady-state latency, or during recovery of the TG-resident memory CD8+ T cell population following stress-, and corticosterone-induced depletion and HSV-1 reactivation from latency. Bromodeoxy uridine (BrdU) incorporation measured cell proliferation in vivo. TAK-779 treatment during acute HSV-1 infection reduced the number of infiltrating CD8+ T cells but did not alter the number of viral genome copies. TAK-779 treatment during HSV latency did not affect the size of the TG-resident memory CD8+ T cell population. Transferred HSV-specific CD8+ T cells failed to access latently infected TG during steady-state latency, or during recovery of the TG resident HSV-specific CD8+ T cell population following exposure of latently infected mice to stress and corticosterone. Recovery of the HSV-specific CD8+ T cell population after stress and corticosterone treatment occurred with homeostatic levels of cell division and did not require CD4+ T cell help. Our findings are consistent with the notion that the CD8+ T cells in latently infected TG are a tissue-resident memory (Trm) population that is maintained without replenishment from the periphery, and that when this population is disrupted, it recovers without proliferation or detectable recruitment of HSV-specific CD8+ T cells from the blood. The compartmentalization of the HSV-specific CD8+ memory T cell population in latently infected TG will complicate the design of therapeutic vaccines.