Pathological effect of IL-17A-producing TCRγδ(+) T cells in mouse genital mucosa against HSV-2 infection.
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.
Mucosal Immunology Section, Laboratory Science Division, International Vaccine Institute, Seoul National University Research Park, Kwanak-Gu, Seoul 151-919, Republic of Korea.
Jae-Ouk
JO
Kim
Hye-Ran
HR
Cha
Eun-Do
ED
Kim
Mi-Na
MN
Kweon
D000818:Animals; D005260:Female; D005836:Genitalia, Female / Q000276:immunology* / Q000821:virology*; D006558:Herpes Genitalis / Q000235:genetics / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D016130:Immunophenotyping; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000276:immunology / Q000821:virology; D010641:Phenotype; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta