Clearance of herpes simplex virus type 2 by CD8+ T cells requires gamma interferon and either perforin- or Fas-mediated cytolytic mechanisms

J Virol. 2005 Dec;79(23):14546-54. doi: 10.1128/JVI.79.23.14546-14554.2005.

Abstract

The T-cell-mediated resolution of herpes simplex virus type 2 (HSV-2) genital infections is not fully understood. In these studies, the mechanisms by which CD8+ T cells clear virus from the genital epithelium were examined. Ovalbumin (OVA)-specific CD8+ T cells from OT-I transgenic mice cleared a thymidine kinase-deficient, ovalbumin-expressing HSV-2 virus (HSV-2 tk- OVA) from the genital epithelium of recipient mice, and clearance was abrogated by in vivo neutralization of gamma interferon (IFN-gamma). Further, CD8+ OT-I T cells deficient in IFN-gamma were unable to clear HSV-2 tk- OVA from the vaginal epithelium. The requirement for cytolytic mechanisms in HSV-2 tk- OVA clearance was tested in radiation chimeras by adoptive transfer of wild-type or perforin-deficient OT-I T cells to irradiated Fas-defective or wild-type recipients. Although a dramatic decrease in viral load was observed early after challenge with HSV-2 tk- OVA, full resolution of the infection was not achieved in recipients lacking both perforin- and Fas-mediated cytolytic pathways. These results suggest that IFN-gamma was responsible for an early rapid decrease in HSV-2 virus titer. However, either perforin- or Fas-mediated cytolytic mechanisms were required to achieve complete clearance of HSV-2 from the genital epithelium.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Herpes Genitalis / immunology*
  • Herpes Genitalis / virology
  • Herpesvirus 2, Human / immunology*
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Knockout
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • T-Lymphocytes, Cytotoxic / immunology*
  • fas Receptor / immunology*

Substances

  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • fas Receptor
  • Perforin