Theil Diethilde, Derfuss Tobias, Paripovic Igor, Herberger Simone, Meinl Edgar, Schueler Olaf, Strupp Michael, Arbusow Viktor, Brandt Thomas
Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany.
Am J Pathol. 2003 Dec;163(6):2179-84. doi: 10.1016/S0002-9440(10)63575-4.
The majority of trigeminal ganglia (TGs) are latently infected with alpha-herpesviruses [herpes simplex virus type-1 (HSV-1) and varicella-zoster virus (VZV)]. Whereas HSV-1 periodically reactivates in the TGs, VZV reactivates very rarely. The goal of this study was to determine whether herpesvirus latency is linked to a local immune cell infiltration in human TGs. T cells positive for the CD3 and CD8 markers, and CD68-positive macrophages were found in 30 of 42 examined TGs from 21 healthy individuals. The presence of immune cells correlated constantly with the occurrence of the HSV-1 latency-associated transcript (LAT) and only irregularly with the presence of latent VZV protein. In contrast, uninfected TGs showed no immune cell infiltration. Quantitative RT-PCR revealed that CD8, interferon-gamma, tumor necrosis factor-alpha, IP-10, and RANTES transcripts were significantly induced in TGs latently infected with HSV-1 but not in uninfected TGs. The persisting lymphocytic cell infiltration and the elevated CD8 and cytokine/chemokine expression in the TGs demonstrate for the first time that latent herpesviral infection in humans is accompanied by a chronic inflammatory process at an immunoprivileged site but without any neuronal destruction. The chronic immune response seems to maintain viral latency and influence viral reactivation.
大多数三叉神经节（TGs）潜伏感染α-疱疹病毒[单纯疱疹病毒1型（HSV-1）和水痘-带状疱疹病毒（VZV）]。HSV-1会在TGs中周期性重新激活，而VZV极少重新激活。本研究的目的是确定疱疹病毒潜伏是否与人类TGs中的局部免疫细胞浸润有关。在来自21名健康个体的42个被检测的TGs中的30个中，发现了CD3和CD8标记阳性的T细胞以及CD68阳性的巨噬细胞。免疫细胞的存在始终与HSV-1潜伏相关转录本（LAT）的出现相关，而与潜伏性VZV蛋白的存在仅偶尔相关。相比之下，未感染的TGs未显示免疫细胞浸润。定量逆转录聚合酶链反应（RT-PCR）显示，在潜伏感染HSV-1的TGs中，CD8、干扰素-γ、肿瘤坏死因子-α、IP-10和调节激活正常T细胞表达和分泌的趋化因子（RANTES）转录本显著诱导，而在未感染的TGs中则未诱导。TGs中持续的淋巴细胞浸润以及CD8和细胞因子/趋化因子表达的升高首次证明，人类潜伏性疱疹病毒感染伴随着免疫特权部位的慢性炎症过程，但没有任何神经元破坏。慢性免疫反应似乎维持病毒潜伏并影响病毒重新激活。
