Selective retention of herpes simplex virus-specific T cells in latently infected human trigeminal ganglia
Selective retention of herpes simplex virus-specific T cells in latently infected human trigeminal ganglia
复制标题
DOI：
10.1073/pnas.0610847104
复制
发表时间：
2007-02-27
影响因子：
11.1
通讯作者：
Osterhaus, Albert D. M. E.
中科院分区：
文献类型：
--
作者：
Verjans, Georges M. G. M.;Hintzen, Rogier Q.;Osterhaus, Albert D. M. E.
单纯疱疹病毒1型（HSV-1）和水痘带状疱疹病毒（VZV）的原发感染导致感觉神经节（如三叉神经节（TG））中神经元的终身潜伏感染。据推测，保留在TG中的T细胞抑制潜伏病毒的再活化。在死亡后数小时内获得个体的TG标本提供了表征人类TG驻留T细胞的表型和特异性的独特机会。发现大量表达晚期效应记忆表型的活化CD 8（+）T细胞存在于潜伏感染的TG中。T细胞浸润是寡克隆的，并且T细胞选择性地聚集在HSV-1周围，但不聚集在VZV潜伏感染的神经元周围。尽管颗粒酶8表达的神经元相互作用的CD 8（+）T细胞没有观察到神经元损伤。TG驻留T细胞，主要是CD 8（+）T细胞，针对HSV-1，而不是VZV，尽管神经元表达VZV蛋白。结果表明，人类TG中的疱疹病毒潜伏期与局部持续性T细胞应答相关，包括活化的晚期效应记忆CD 8（+）T细胞，这些细胞似乎通过非细胞溶解途径控制HSV-1潜伏期。相反，T细胞似乎不直接参与控制人TG中的VZV潜伏期。
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 8 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.