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Herpes simplex virus (HSV)-specific T cells are essential to control and resolve genital herpes (GH). To investigate the potential involvement of γδ T cells in GH, T cells were recovered and expanded, by mitogenic stimulation, to T cell lines from the genital lesions of 17 patients with GH and 5 control subjects who had other diseases. Relatively high numbers of γδ T cells—predominantly, Vγ9Vδ2 T cells—were detected only in the T cell lines of the patients with GH. Intralesional Vγ9Vδ2 T cell clones did not recognize HSV-infected cells, but they showed reactivity to isopentenyl pyrophosphate and Daudi cells. The T cell clones secreted interferon-γ tumor necrosis factor-α, interleukin (IL)-8, macrophage inflammatory protein-1α, and RANTES (regulated on activation, normally T cell expressed or secreted), but they secreted no or limited IL-4. The results of the present study suggest the infiltration and putative involvement of isopentenyl pyrophosphate-reactive Vγ9Vδ2 T helper 1-like cells in individuals with GH. [ABSTRACT FROM AUTHOR]

Intraocular infection with herpes simplex virus (HSV) can cause uveitis, a potentially sightthreatening disease. The disease is characterized by an ocular infiltration of inflammatory cells such as macrophages and B and T cells. The characteristics of the local humoral and cellular immune responses elicited on intraocular HSV infection are poorly understood. The local HSV-specific antibody production, which are used routinely for confirmation of a clinical diagnosis of herpetic uveitis, has never been analyzed in detail. This study analyzed the humoral immune response against HSV type 1 (HSV-1) in paired samples of intraocular fluid and serum of patients with intraocular herpesvirus infection. In addition, the B cell epitope distribution on a single HSV-1 type-specific antigen, glycoprotein G, was compared for these paired samples. The results presented here indicate that the inflamed eyes of patients with HSV-induced uveitis display a compartmentalized B cell response directed toward the triggering virus. [ABSTRACT FROM AUTHOR]

Elucidates the target antigens and the epitopes recognized by such T cell clones (TCC) from three patients with herpes simplex virus type 1 (HSV-1)-induced acute retinal necrosis. Analysis of the fine specificities of genetically different T cell clones with recombinant HSV viruses and synthetic peptides; Identification of the target antigen; Identification of two separate CD4[sup +] VP13/14 T cell epitopes.

Abstract: Background: Acyclovir (ACV) is the antiviral drug of choice to treat patients with herpes simplex virus type 1 (HSV-1) uveitis. The prevalence of intra-ocular ACV-resistant (ACVR) HSV-1 in herpetic uveitis is unknown and may have clinical consequences. In addition to its predictive value on ACV susceptibility, the polymorphic HSV-1 thymidine kinase (TK) gene facilitates differentiation between HSV-1 strains. Objectives: The objective of this study was to determine the genetic composition and ACV susceptibility of the causative virus in intra-ocular fluid samples (IOF) of HSV-1 uveitis patients. Study design: The intra-ocular HSV-1 pool from 11 HSV-1 uveitis patients was determined by sequencing IOF-derived viral TK genes. The ACV susceptibility profile of the cloned intra-ocular TK variants was defined by mass spectrometry. In addition, the ganciclovir (GCV) susceptibility of the ACVR HSV-1 TK variants was defined. Results: Intra-ocular fluid samples of HSV-1 uveitis patients contain HSV-1 quasispecies, principally consisting of one major and multiple genetically related minor patient-specific TK variants. Four of 10 patients analyzed had an intra-ocular ACVR HSV-1 of which 3 were cross-resistant to GCV. The ACVR profile of intra-ocular HSV-1 did not correlate with symptomatic ACV treatment. Conclusions: Affected eyes of HSV-1 uveitis patients are commonly infected with a patient-specific HSV-1 quasispecies, including one major and multiple genetically related minor variants. A relatively high prevalence of intra-ocular ACVR HSV-1, mainly ACV/GCV cross-resistant viruses, was detected in HSV-1 uveitis patients. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]