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

The role of B, CD4(+) T and CD8(+) T cells in both primary genital infectio n with attenuated herpes simplex virus type 2 (HSV-2) and development of pr otective immunity to a later challenge with virulent HSV-2 using lymphocyte -deficient mice has been elucidated. Following primary inoculation with att enuated thymidine kinase-deficient (TK-) HSV-2, B cell-deficient (mu MT) mi ce developed a local viraemia and transient genital inflammation, suggestin g a role for B cells in the innate control of local infection and inflammat ion. Natural antibodies are implicated in this process, as passive transfer of normal serum into mu MT mice significantly reduced HSV-2 TK- shedding i n the vaginal lumen, although it did not affect subsequent inflammation. Pr otection against lethal HSV-2 challenge was noted in HSV-2-vaccinated wild- type, CD8(+) T cell-deficient and mu MT mice and was characterized by stron g virus-specific IFN-gamma responses in vitro and delayed type hypersensiti vity (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 respo nses to HSV-2 could be induced in HSV-2-vaccinated CD4(-/-) mice by treatme nt with recombinant IFN-gamma, Taken together, these results suggest that C D4(+) T cells secreting IFN-gamma are critical for immune protection agains t lethal genital HSV-2 re-infection, whereas B cells/natural antibodies hav e anti-viral and -inflammatory effects in the innate control of a primary i nfection.