Liu T, Tang Q, Hendricks R L
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago 60612, USA.
J Virol. 1996 Jan;70(1):264-71. doi: 10.1128/JVI.70.1.264-271.1996.
Following herpes simplex virus type 1 (HSV-1) infection of the cornea, the virus is transmitted to the trigeminal ganglion, where a brief period of virus replication is followed by establishment of a latent infection in neurons. A possible role of the immune system in regulating virus replication and maintaining latency in the sensory neurons has been suggested. We have investigated the phenotype and cytokine pattern of cells that infiltrate the A/J mouse trigeminal ganglion at various times after HSV-1 corneal infection. HSV antigen expression in the trigeminal ganglion (indicative of the viral lytic cycle) increased until day 3 postinfection (p.i.) and then diminished to undetectable levels by day 7 p.i. The period of declining HSV antigen expression. was associated with a marked increase in Mac-1+ cells. These cells did not appear to coexpress the F4/80+ (macrophage) or the CD8+ (T cell) markers, and none showed polymorphonuclear leukocyte morphology, suggesting a possible early infiltration of natural killer cells. There was also a significant increase in the trigeminal ganglion of cells expressing the gamma delta T-cell receptor, and these cells were found almost exclusively in very close association with neurons. This period was also characterized by a rapid and equivalent increase in cells expressing gamma interferon and interleukin-4. The density of the inflammatory infiltrate in the trigeminal ganglion increased until days 12 to 21 p.i., when it was predominated by CD8+, Mac-1+, and tumor necrosis factor-expressing cells, which surrounded many neurons. By day 92 p.i., the inflammatory infiltrate diminished but was heaviest in mice with active periocular skin disease. Our data are consistent with the notion that gamma interferon produced by natural killer cells and/or gamma delta T cells may play an important role in limiting HSV-1 replication in the trigeminal ganglion during the acute stage of infection. In addition, tumor necrosis factor produced by CD8+ T cells and macrophages may function to maintain the virus in a latent state.
在单纯疱疹病毒1型（HSV-1）感染角膜后，病毒会传播至三叉神经节，在那里会有一段短暂的病毒复制期，随后在神经元中建立潜伏感染。免疫系统在调节病毒复制以及维持感觉神经元潜伏感染方面可能发挥作用，这一观点已被提出。我们研究了HSV-1角膜感染后不同时间点浸润A/J小鼠三叉神经节的细胞的表型和细胞因子模式。三叉神经节中HSV抗原表达（指示病毒裂解周期）在感染后第3天（p.i.）前持续增加，然后在感染后第7天降至无法检测的水平。HSV抗原表达下降的时期与Mac-1+细胞显著增加相关。这些细胞似乎不共表达F4/80+（巨噬细胞）或CD8+（T细胞）标志物，且均未表现出多形核白细胞形态，提示可能有自然杀伤细胞早期浸润。表达γδ T细胞受体的细胞在三叉神经节中也显著增加，且这些细胞几乎仅在与神经元紧密相邻处被发现。这一时期的特征还包括表达γ干扰素和白细胞介素-4的细胞迅速且等量增加。三叉神经节中的炎性浸润密度在感染后第12至21天持续增加，此时以围绕许多神经元的CD8+、Mac-1+和表达肿瘤坏死因子的细胞为主。到感染后第92天，炎性浸润减少，但在患有活动性眼周皮肤疾病的小鼠中最为严重。我们的数据与以下观点一致：自然杀伤细胞和/或γδ T细胞产生的γ干扰素可能在感染急性期限制HSV-1在三叉神经节中的复制方面发挥重要作用。此外，CD8+ T细胞和巨噬细胞产生的肿瘤坏死因子可能起到使病毒维持潜伏状态的作用。
