Abstract
Objectives Genital herpes simplex virus (HSV) infection is controlled by HSV-specific T cells in the genital tract, and the role of systemic T cell responses is not fully understood. Thus, we analysed T cell responses in patients with recurrent genital herpes (GH). Methods T cell responses to HSV-1 and HSV-2 native antigens and the expression of HLA-DR and CD38 molecules on circulating CD8+ T cells were analysed in adults with high frequency of GH recurrences (19 patients) and low frequency of GH recurrences (7 patients) and 12 HSV-2 seronegative healthy controls. The study utilized the interferon-γ Elispot assay for measurement of spot-forming cells (SFC) after ex vivo stimulation with HSV antigens and flow cytometry for analysis of the expression of activation markers in unstimulated T cells. Results The patients with high frequency of GH recurrences (mean number of recurrences of 13.3 per year) had significantly enhanced HSV-specific T cell responses than the HSV-2 seronegative healthy controls. Moreover, a trend of higher numbers of SFC was observed in these patients when compared with those with low frequency of GH recurrences (mean number of recurrences of 3.3 per year). Additionally, no differences in CD38 and HLA-DR expression on circulating CD8+ T cells were found among the study groups. Conclusions Frequency of GH recurrences positively correlates with high numbers of systemic HSV-specific T cells.
Highlights
Genital herpes (GH) represents an important health problem. e disease is caused by herpes simplex virus (HSV) type 1 or type 2 entering the body through the genital tract of a nonimmune person
We evaluated HSV-specific T cell responses and the expression of immune activation markers on peripheral CD8+ T cells in blood from patients with recurrent GH. e IFN-c Elispot assay was used because it has high sensitivity for the detection of specific T cells and is simple and reproducible [10]
We observed a positive correlation of HSVspecific T cells with frequency of GH recurrences; the recurrences were not associated with changes in expression of activation markers on peripheral CD8+ T cells
Summary
Genital herpes (GH) represents an important health problem. e disease is caused by herpes simplex virus (HSV) type 1 or type 2 entering the body through the genital tract of a nonimmune person. After the primary HSV infection, the virus stays dormant in the dorsal nerve root ganglia. In some individuals with latent infection, the virus reactivates several times yearly and the reactivation may lead to either recurrent GH or asymptomatic genital shedding of HSV-2 [1]. E latency of HSV in the dorsal nerve root ganglia is maintained by viral, cell, and immune mechanisms [2]. Specific CD8+ T cells are the most important immune cell types in providing immune surveillance in the tissues because in situ hybridization studies revealed their localization in latently infected ganglia and in the proximity of sensory nerve endings in the skin of genitalia of patients with recurrent GH [3,4]. Some studies suggest a role of HSVspecific CD4+ T cells because genital ulcerations caused by HSV-2 are heavily infiltrated by this cell type [5]
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