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 Milligan

Research output: Contribution to journalArticle

55 Citations (Scopus)

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
Pages (from-to)14546-14554
Number of pages9
JournalJournal of Virology
Volume79
Issue number23
DOIs
StatePublished - Dec 2005

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Human herpesvirus 2
Human Herpesvirus 2
interferon-gamma
Interferon-gamma
ovalbumin
Ovalbumin
T-lymphocytes
T-Lymphocytes
genitalia
epithelium
Epithelium
Perforin
interferons
viral load
Viral Load
Interferons
Radiation Chimera
Viruses
thymidine kinase
Herpes Genitalis

ASJC Scopus subject areas

  • Immunology

Cite this

Clearance of herpes simplex virus type 2 by CD8+ T cells requires gamma interferon and either perform- or Fas-mediated cytolytic mechanisms. / Dobbs, Melanie E.; Strasser, Jane E.; Chu, Chin Fun; Chalk, Claudia; Milligan, Gregg.

In: Journal of Virology, Vol. 79, No. 23, 12.2005, p. 14546-14554.

Research output: Contribution to journalArticle

Dobbs, Melanie E. ; Strasser, Jane E. ; Chu, Chin Fun ; Chalk, Claudia ; Milligan, Gregg. / Clearance of herpes simplex virus type 2 by CD8+ T cells requires gamma interferon and either perform- or Fas-mediated cytolytic mechanisms. In: Journal of Virology. 2005 ; Vol. 79, No. 23. pp. 14546-14554.
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