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Journal of General Virology (2001), 82, 845-853.
© 2001 Society for General Microbiology

Animal: DNA Viruses

Differential roles of B cells and IFN-{gamma}-secreting CD4+ T cells in innate and adaptive immune control of genital herpes simplex virus type 2 infection in mice

Ali M. Harandi1, Bo Svennerholm2, Jan Holmgren1 and Kristina Eriksson1

Departments of Medical Microbiology and Immunology1 and Clinical Virology2, Göteborg University, Guldhedsgatan 10A, 413 46 Göteborg, Sweden

Author for correspondence: Kristina Eriksson. Fax +46 31 820160. e-mail kristina.eriksson{at}microbio.gu.se

The role of B, CD4+ T and CD8+ T cells in both primary genital infection with attenuated herpes simplex virus type 2 (HSV-2) and development of protective immunity to a later challenge with virulent HSV-2 using lymphocyte-deficient mice has been elucidated. Following primary inoculation with attenuated thymidine kinase-deficient (TK-) HSV-2, B cell-deficient (µMT) mice developed a local viraemia and transient genital inflammation, suggesting a role for B cells in the innate control of local infection and inflammation. Natural antibodies are implicated in this process, as passive transfer of normal serum into µMT mice significantly reduced HSV-2 TK- shedding in the vaginal lumen, although it did not affect subsequent inflammation. Protection against lethal HSV-2 challenge was noted in HSV-2-vaccinated wild-type, CD8+ T cell-deficient and µMT mice and was characterized by strong virus-specific IFN-{gamma} responses in vitro and delayed type hypersensitivity (DTH) responses in vivo. In contrast, CD4+ T cell-deficient (CD4-/-) mice had impaired HSV-2-specific IFN-{gamma} production and DTH responses and succumbed rapidly to genital HSV-2 challenge. However, protective responses to HSV-2 could be induced in HSV-2-vaccinated CD4-/- mice by treatment with recombinant IFN-{gamma}. Taken together, these results suggest that CD4+ T cells secreting IFN-{gamma} are critical for immune protection against lethal genital HSV-2 re-infection, whereas B cells/natural antibodies have anti-viral and -inflammatory effects in the innate control of a primary infection.




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