title: Characterization of the varicella zoster virus (VZV)-specific intra-ocular T-cell response in patients with VZV-induced uveitis.
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.
authors.affiliation: Institute of Virology, Erasmus Medical Center, PO Box 1738, 3000 DR, Rotterdam, The Netherlands.
authors.forename: Johannes C M
authors.initials: JC
authors.lastname: Milikan
authors.forename: Robert W A M
authors.initials: RW
authors.lastname: Kuijpers
authors.forename: G Seerp
authors.initials: GS
authors.lastname: Baarsma
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.forename: Georges M G M
authors.initials: GM
authors.lastname: Verjans
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000276:immunology; D001082:Aqueous Humor / Q000276:immunology; D002460:Cell Line; D004279:DNA, Viral / Q000032:analysis; D005123:Eye / Q000276:immunology* / Q000821:virology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006562:Herpes Zoster / Q000276:immunology*; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014605:Uveitis / Q000276:immunology / Q000821:virology*
chemical_list: D000956:Antigens, Viral; D004279:DNA, Viral; D016693:Receptors, Antigen, T-Cell, alpha-beta