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 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 (microMT) 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 microMT 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 microMT 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.
Departments of Medical Microbiology and Immunology1 and Clinical Virology2, Göteborg University, Guldhedsgatan 10A, 413 46 Göteborg, Sweden.
Ali M
AM
Harandi
Departments of Medical Microbiology and Immunology1 and Clinical Virology2, Göteborg University, Guldhedsgatan 10A, 413 46 Göteborg, Sweden.
Bo
B
Svennerholm
Departments of Medical Microbiology and Immunology1 and Clinical Virology2, Göteborg University, Guldhedsgatan 10A, 413 46 Göteborg, Sweden.
Jan
J
Holmgren
Departments of Medical Microbiology and Immunology1 and Clinical Virology2, Göteborg University, Guldhedsgatan 10A, 413 46 Göteborg, Sweden.
Kristina
K
Eriksson
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D001402:B-Lymphocytes / Q000502:physiology*; D015704:CD4 Antigens / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000209:etiology; D007371:Interferon-gamma / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014611:Vaccination; D014779:Virus Replication
D000914:Antibodies, Viral; D015704:CD4 Antigens; D016207:Cytokines; D007371:Interferon-gamma