The role of gamma interferon in immune resistance to vaginal infection by herpes simplex virus type 2 in mice

Abstract

We investigated the role of interferon gamma (IFN-γ) in a mouse model of immunity to vaginal infection by herpes simplex virus type 2 (HSV-2). Within 8 h after immune mice were challenged intravaginally with HSV-2, IFN- γ concentrations in vaginal secretions reached levels that can be antiviral in vitro. This rapid synthesis of IFN-γ occurred in immune-challenged mice but not in nonimmune-challenged mice, indicating that it required memory T cells. Immunostaining and in situ hybridization revealed that the IFN-γ was synthesized by cells whose morphological appearance suggested that they were lymphocytes and macrophage-like cells in the mucosa. The presence of IFN-γ in vaginal secretions was correlated with upregulation of MHC class II antigens in the epithelium and with vigorous (30-fold) recruitment of T and B lymphocytes into the vagina. In vivo administration of anti-IFN-γ to immune mice 17 h before virus challenge blocked the subsequent appearance of IFN-γ in vaginal secretions, blocked upregulation of class II antigens, blocked adherence of T cells to endothelium and their recruitment into the vagina, and markedly reduced immunity against reinfection of the vaginal epithelium.