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Division of Infectious Diseases, Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229
Intravaginal inoculation of mice with an attenuated strain of
herpes simplex virus type 2 (HSV-2) resulted in vigorous HSV-specific
immune responses that protected against subsequent challenge with fully
virulent HSV-2 strains. Even in the presence of high titers of
HSV-specific Ab, T cell-dependent mechanisms were required for
protection of the vaginal mucosae of HSV-immune mice and could be
detected by 24 h after intravaginal reinoculation. Depletion of
specific T cell subsets from HSV-immune mice before HSV-2 reinoculation
demonstrated that CD4+ T cells were primarily
responsible for this protection. Similarly, optimal protection of the
sensory ganglia against reinfection with HSV-2 was dependent on the
presence of T cells. Infectious HSV-2 was not detected in the sensory
ganglia or spinal cord of HSV-immune mice depleted of only
CD4+ or CD8+ T cells, suggesting that the T
cell-mediated protection could be provided by either subset. Similarly,
neutralization of IFN-
during challenge of HSV-immune mice resulted
in diminished protection of the vaginal mucosa, but not of the sensory
ganglia. These results suggest that the ability to induce vigorous
HSV-specific T cell responses is an important consideration in the
design of vaccines to protect both the vaginal mucosa and sensory
ganglia against HSV-2.
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