重新评估CD8 T细胞对1型单纯疱疹病毒的反应:对亚显性表位有反应的CD8 T细胞的参与

Reevaluating the CD8 T-cell response to herpes simplex virus type 1: involvement of CD8 T cells reactive to subdominant epitopes.

作者信息

Sheridan Brian S, Cherpes Thomas L, Urban Julie, Kalinski Pawel, Hendricks Robert L

机构信息

Graduate Program in Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

出版信息

J Virol. 2009 Mar;83(5):2237-45. doi: 10.1128/JVI.01699-08. Epub 2008 Dec 10.

Abstract

In C57BL/6 (B6) mice, most herpes simplex virus (HSV)-specific CD8 T cells recognize a strongly immunodominant epitope on glycoprotein B (gB498) and can inhibit HSV type 1 (HSV-1) reactivation from latency in trigeminal ganglia (TG). However, half of the CD8 T cells retained in latently infected TG of B6 mice are not gB498 specific and have been largely ignored. The following observations from our current study indicate that these gB498-nonspecific CD8 T cells are HSV specific and may contribute to the control of HSV-1 latency. First, following corneal infection, OVA257-specific OT-1 CD8 T cells do not infiltrate the infected TG unless mice are simultaneously immunized with OVA257 peptide, and then they are not retained. Second, 30% of CD8 T cells in acutely infected TG that produce gamma interferon in response to HSV-1 stimulation directly ex vivo are gB498 nonspecific, and these cells maintain an activation phenotype during viral latency. Finally, gB498-nonspecific CD8 T cells are expanded in ex vivo cultures of latently infected TG and inhibit HSV-1 reactivation from latency in the absence of gB498-specific CD8 T cells. We conclude that many of the CD8 T cells that infiltrate and are retained in infected TG are HSV specific and potentially contribute to maintenance of HSV-1 latency. Identification of the viral proteins recognized by these cells will contribute to a better understanding of the dynamics of HSV-1 latency.

摘要

在C57BL/6(B6)小鼠中,大多数单纯疱疹病毒(HSV)特异性CD8 T细胞识别糖蛋白B(gB498)上一个强免疫显性表位,并能抑制三叉神经节(TG)中1型单纯疱疹病毒(HSV-1)从潜伏状态重新激活。然而,保留在B6小鼠潜伏感染TG中的CD8 T细胞有一半不是gB498特异性的,并且在很大程度上被忽视了。我们当前研究的以下观察结果表明,这些gB498非特异性CD8 T细胞是HSV特异性的,可能有助于控制HSV-1潜伏。首先,角膜感染后,OVA257特异性OT-1 CD8 T细胞不会浸润感染的TG,除非小鼠同时用OVA257肽免疫,然后它们不会被保留。其次,在急性感染的TG中,直接在体外对HSV-1刺激产生γ干扰素的CD8 T细胞中有30%是gB498非特异性的,并且这些细胞在病毒潜伏期间保持激活表型。最后,gB498非特异性CD8 T细胞在潜伏感染TG的体外培养中扩增,并在没有gB498特异性CD8 T细胞时抑制HSV-1从潜伏状态重新激活。我们得出结论,浸润并保留在感染TG中的许多CD8 T细胞是HSV特异性的,可能有助于维持HSV-1潜伏。鉴定这些细胞识别的病毒蛋白将有助于更好地理解HSV-1潜伏的动态变化。

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