T-cell-mediated mechanisms involved in resolution of genital herpes simplex virus type 2 (HSV-2) infection of mice

Resolution of a HSV-2 infection of the female genital tract has been shown to be T-cell dependent. The T-cell populations and mechanisms involved in clearance of virus from the genital epithelium were examined in this study. T lymphocytes expressing either alphabeta or gammadelta T-cell receptors (TCR) have been detected in the vaginal epithelium of mice. The involvement of gammadelta T cells in HSV-2 clearance was tested by intravaginal (ivag) challenge of mice depleted of alphabeta T cells by administration of specific antibodies and of mice lacking yb T cells due to specific deletion of the delta TCR gene. The results of these studies strongly suggest that gammadelta T cells are not required for or involved in clearance of HSV-2 from the genital epithelium. Mechanisms of virus clearance employed by alphabeta T cells were also examined. Although HSV-specific lytic activity could be demonstrated ex vivo in populations of vaginal exudate cells from HSV-infected mice, clearance of virus did not require either perforin- or Fas/Fas ligand (FasL) -dependent cytolytic pathways. In contrast, virus resolution was significantly impaired following neutralization of interferon-gamma (IFN-gamma), but not tumor necrosis factor-alpha (TNF-alpha). Together, these results suggest that non-lytic mechanisms mediated by alphabeta T cells were responsible for resolution of a genital HSV-2 infection. (C) 2004 Elsevier Ireland Ltd. All rights reserved.