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Journal of Virology, December 2005, p. 14546-14554, Vol. 79, No. 23
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.23.14546-14554.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Clearance of Herpes Simplex Virus Type 2 by CD8⁺ T Cells Requires Gamma Interferon and either Perforin- or Fas-Mediated Cytolytic Mechanisms

Department of Pathology,¹ Department of Pediatrics,³ Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas 77555,⁴ Children's Hospital Research Foundation, Cincinnati, Ohio 45229²

Received 5 July 2005/ Accepted 16 September 2005

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-). Further, CD8⁺ OT-I T cells deficient in IFN- 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- 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.

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