Analysis of herpes simplex virus-specific T cells in the murine female genital tract following genital infection with herpes simplex virus type 2.
A murine model of genital infection with a thymidine kinase-deficient (tk-) strain of herpes simplex virus type 2 (HSV-2) was utilized to examine the development of the local T cell response in the genital mucosa and draining genital lymph nodes (gLN). HSV-specific cytokine-secreting T cells were detected in the gLN 4 days postintravaginal inoculation but not in the urogenital tract or spleen until 5 days postinoculation, suggesting the cellular immune response originates in the gLN. More CD4+ than CD8+ gLN T cells were detected by flow cytometric analysis following primary vaginal inoculation and the majority of HSV-specific gLN T cells detected by ELISPOT were CD4+ and Th1-like based on secretion of IFN gamma and not IL-4 or IL-5. A similar population of HSV-specific memory T cells persisted in the genital tract 2 months following HSV-2 tk- genital inoculation. These data suggest that the urogenital cellular immune response elicited in mice following genital inoculation with HSV-2 tk- is predominantly CD4+ and Th1-like, resembling that observed in humans. The results of this study are important for the rational design of vaccines capable of inducing protective immunity in the genital tract.
Milligan
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Division of Clinical Virology, James N. Gamble Institute of Medical Research, Cincinnati, Ohio 45219, USA.
Bernstein
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DI
D000818:Animals; D017252:CD3 Complex / Q000032:analysis; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005836:Genitalia, Female / Q000276:immunology* / Q000821:virology; D006558:Herpes Genitalis / Q000276:immunology* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000276:immunology / Q000821:virology; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
D017252:CD3 Complex; D007371:Interferon-gamma