title: T-cell-mediated mechanisms involved in resolution of genital herpes simplex virus type 2 (HSV-2) infection of mice.
abstract: 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 gammadelta 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.
authors.affiliation: Department of Pediatrics, Children's Hospital Research Foundation, Cincinnati, OH, USA. gnmillig@utmb.edu
authors.forename: Gregg N
authors.initials: GN
authors.lastname: Milligan
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Dudley-McClain
authors.forename: Christal G
authors.initials: CG
authors.lastname: Young
authors.forename: Chin-Fun
authors.initials: CF
authors.lastname: Chu
mesh_terms: D000818:Animals; D016923:Cell Death / Q000276:immunology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology; D053222:Fas Ligand Protein; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000276:immunology*; D018928:Immunity, Mucosal; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014621:Vagina / Q000166:cytology / Q000276:immunology / Q000821:virology; D019014:fas Receptor / Q000276:immunology
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D054353:Perforin; D007371:Interferon-gamma