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

Melanie E. Dobbs, Jane E. Strasser, Chin Fun Chu, Claudia Chalk, Gregg N. Milligan

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

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-γ). Further, CD8+ OT-I T cells deficient in IFN-γ 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 perform- and Fas-mediated cytolytic pathways. These results suggest that IFN-γ 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.

Original languageEnglish (US)
Pages (from-to)14546-14554
Number of pages9
JournalJournal of virology
Volume79
Issue number23
DOIs
StatePublished - Dec 2005

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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