Abstract
Interleukin (IL)-17A is a cytokine that plays an important role in infectious, autoimmune, and inflammatory diseases. In this study, we found that TCRγδ(+)CD4(-)CD8(-) T cells, but not TCRαβ(+)CD4(+) T cells, are the primary producers of IL-17A in the genital tract of female mice in the steady-state condition. High mRNA levels of IL-17A and RORγt were determined in TCRγδ(+) T cells isolated from mouse genital tract but lacked detectable expression of IFNγ, T-bet, and FoxP3. IL-17A production by genital TCRγδ(+) T cells was maintained after intravaginal vaccination with cholera toxin or avirulent herpes simplex virus type (HSV)-2 186 syn ΔTK strain. Of note, the deaths of IL-17A(-/-) mice were significantly delayed after intravaginal HSV-2 infection compared with wild-type mice. Further, genital TCRγδ(+) T cells continued to produce comparable amounts of IL-17A after antibiotic treatment. These results imply that genital IL-17A-producing TCRγδ(+) T cells constitutively exist at steady state and that they play a pathogenic effect against HSV-2 infection and are not affected by microflora, unlike conventional Th17 cells.