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水痘带状疱疹病毒(VZV)诱导性葡萄膜炎患者中VZV特异性眼内T细胞反应的特征分析

Characterization of the varicella zoster virus (VZV)-specific intra-ocular T-cell response in patients with VZV-induced uveitis.

作者信息

Milikan Johannes C M, Kuijpers Robert W A M, Baarsma G Seerp, Osterhaus Albert D M E, Verjans Georges M G M

机构信息

Institute of Virology, Erasmus Medical Center, PO Box 1738, 3000 DR, Rotterdam, The Netherlands.

出版信息

Exp Eye Res. 2006 Jul;83(1):69-75. doi: 10.1016/j.exer.2005.11.008. Epub 2006 Mar 10.

Abstract

Varicella zoster virus (VZV) is a well-known cause of infectious uveitis. The aim of this study was to characterize the VZV-specific T-cell response in eyes of patients with VZV-induced uveitis. T-cell lines (TCL) were generated by mitogenic stimulation of intra-ocular fluid (IOF) samples obtained from eight patients with VZV-induced uveitis. Two patients with herpes simplex virus (HSV)-induced uveitis were included as disease controls. Characterization of individual T-cells in the TCL was performed by stimulating the TCL with mock, HSV-1 and VZV antigen pulsed autologous B cells and subsequent flow cytometric analyses. Virus specificity and phenotype of the T-cells were identified by simultaneous detection of intracellular gamma interferon and cell surface markers CD4, CD8, CD3 or T-cell receptor (TCR) beta chain variable region (TCRBV) usage. The TCL obtained from patients with HSV-1-induced uveitis contained higher numbers of T-cells reactive to HSV-1 compared to VZV. VZV-specific T-cells were detected in all TCL of the patients diagnosed with VZV-induced uveitis. Four out of six TCL obtained from patients with VZV-induced uveitis that were assayed for both viruses, contained higher numbers of T-cells reactive to VZV compared to HSV-1. Detailed analyses of the TCL of two patients demonstrated that the VZV reactivity within the assayed TCL was dominated by T-cells expressing one specific TCRBV gene. The data implicate that VZV-reactive T-cells infiltrate and participate in the local inflammatory response in eyes of patients with VZV-induced uveitis.

摘要

水痘带状疱疹病毒(VZV)是感染性葡萄膜炎的一个众所周知的病因。本研究的目的是对VZV诱导的葡萄膜炎患者眼中的VZV特异性T细胞反应进行特征分析。通过对从8例VZV诱导的葡萄膜炎患者获得的眼内液(IOF)样本进行丝裂原刺激来生成T细胞系(TCL)。将2例单纯疱疹病毒(HSV)诱导的葡萄膜炎患者作为疾病对照。通过用模拟物、HSV-1和VZV抗原脉冲的自体B细胞刺激TCL并随后进行流式细胞术分析,对TCL中的单个T细胞进行特征分析。通过同时检测细胞内γ干扰素和细胞表面标志物CD4、CD8、CD3或T细胞受体(TCR)β链可变区(TCRBV)的使用情况来鉴定T细胞的病毒特异性和表型。与VZV相比,从HSV-1诱导的葡萄膜炎患者获得的TCL中含有更多对HSV-1有反应的T细胞。在所有被诊断为VZV诱导的葡萄膜炎患者的TCL中均检测到VZV特异性T细胞。在对两种病毒都进行检测的6例VZV诱导的葡萄膜炎患者获得的TCL中,有4例含有比HSV-1更多的对VZV有反应的T细胞。对2例患者的TCL进行的详细分析表明,所检测的TCL中的VZV反应性由表达一个特定TCRBV基因的T细胞主导。这些数据表明,VZV反应性T细胞浸润并参与VZV诱导的葡萄膜炎患者眼中的局部炎症反应。

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