Verjans Georges M G M, Hintzen Rogier Q, van Dun Jessica M, Poot Angelique, Milikan Johannes C, Laman Jon D, Langerak Anton W, Kinchington Paul R, Osterhaus Albert D M E
Department of Virology, Erasmus Medical Center, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.
Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3496-501. doi: 10.1073/pnas.0610847104. Epub 2007 Feb 20.
Primary infection with herpes simplex virus 1 (HSV-1) and varicella zoster virus (VZV) results in lifelong latent infections of neurons in sensory ganglia such as the trigeminal ganglia (TG). It has been postulated that T cells retained in TG inhibit reactivation of latent virus. The acquisition of TG specimens of individuals within hours after death offered the unique opportunity to characterize the phenotype and specificity of TG-resident T cells in humans. High numbers of activated CD8(+) T cells expressing a late effector memory phenotype were found to reside in latently infected TG. The T cell infiltrate was oligoclonal, and T cells selectively clustered around HSV-1 but not VZV latently infected neurons. Neuronal damage was not observed despite granzyme B expression by the neuron-interacting CD8(+) T cells. The TG-resident T cells, mainly CD8(+) T cells, were directed against HSV-1 and not to VZV, despite neuronal expression of VZV proteins. The results implicate that herpesvirus latency in human TG is associated with a local, persistent T cell response, comprising activated late effector memory CD8(+) T cells that appear to control HSV-1 latency by noncytolytic pathways. In contrast, T cells do not seem to be directly involved in controlling VZV latency in human TG.
单纯疱疹病毒1型（HSV-1）和水痘带状疱疹病毒（VZV）的原发性感染会导致感觉神经节（如三叉神经节（TG））中的神经元发生终身潜伏感染。据推测，保留在TG中的T细胞可抑制潜伏病毒的再激活。在个体死亡后数小时内获取TG标本，为表征人类TG驻留T细胞的表型和特异性提供了独特的机会。研究发现，大量表达晚期效应记忆表型的活化CD8(+) T细胞存在于潜伏感染的TG中。T细胞浸润是寡克隆性的，并且T细胞选择性地聚集在HSV-1而非VZV潜伏感染的神经元周围。尽管与神经元相互作用的CD8(+) T细胞表达颗粒酶B，但未观察到神经元损伤。尽管VZV蛋白在神经元中表达，但TG驻留T细胞（主要是CD8(+) T细胞）针对的是HSV-1而非VZV。这些结果表明，人类TG中的疱疹病毒潜伏与局部持续性T细胞反应相关，该反应包括活化的晚期效应记忆CD8(+) T细胞，它们似乎通过非细胞溶解途径控制HSV-1潜伏。相比之下，T细胞似乎并未直接参与控制人类TG中的VZV潜伏。
