Clearance of herpes simplex virus type 2 by CD8+ T cells requires gamma interferon and either perforin- or Fas-mediated cytolytic mechanisms.
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.
Dobbs
Melanie E
ME
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Strasser
Jane E
JE
Chu
Chin-Fun
CF
Chalk
Claudia
C
Milligan
Gregg N
GN
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006558:Herpes Genitalis / Q000276:immunology* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology*
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor; D054353:Perforin