Protective immunity to genital herpes simplex [correction of simpex] virus type 2 infection is mediated by T-bet.
We show, for the first time, that the transcription factor T-bet, which is implicated in IFN-gamma production, is required for the induction of vaccine-induced antiviral immune protection. T-bet was found to be important in both the innate and acquired immune protection against genital HSV-2 infection. T-bet(-/-) and T-bet(+/+) mice were infected vaginally with HSV-2 and examined daily for disease and mortality. T-bet(-/-) mice had significantly higher virus titers than T-bet(+/+) mice following a primary HSV-2 infection, and succumbed significantly earlier to the infection. This result was associated with an impaired NK cell cytotoxic capacity and NK cell-mediated IFN-gamma production in the T-bet(-/-) mice. To assess the induction of acquired antiviral immune protection, mice were vaccinated with an attenuated virus before infection. Vaccinated T-bet(-/-) mice could not control viral replication following an HSV-2 challenge and had significantly higher virus titers and mortality rates than vaccinated T-bet(+/+) mice that remained healthy. The impaired acquired immune protection in T-bet(-/-) mice was associated with a significantly decreased HSV-2-specific delayed-type hypersensitivity response and a significantly reduced HSV-2-specific IFN-gamma production from CD4(+) T cells. However, T-bet deficiency did not impair either the IFN-gamma production or the cytotoxic capacity of HSV-2-specific CD8(+) T cells. We conclude that T-bet plays a crucial role in both the innate defense and the generation of vaccine-induced immunity against genital HSV-2 infection in mice.
Svensson
Alexandra
A
Department of Rheumatology and Inflammation Research, Göteborg University, Göteborg, Sweden.
Nordström
Inger
I
Sun
Jia-Bin
JB
Eriksson
Kristina
K
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D016466:CHO Cells; D006224:Cricetinae; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006558:Herpes Genitalis / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D022301:Herpes Simplex Virus Vaccines / Q000008:administration & dosage / Q000276:immunology; D018258:Herpesvirus 2, Human / Q000276:immunology*; D007110:Immunity, Active / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology / Q000401:mortality; D007694:Killer Cells, Natural / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D020825:T-Box Domain Proteins; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication / Q000235:genetics / Q000276:immunology; D000098815:T-bet Transcription Factor
D000914:Antibodies, Viral; D018984:Epitopes, T-Lymphocyte; D022301:Herpes Simplex Virus Vaccines; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors