CD8+ Tc1 and TIL-17 cells mediate allergic contact hypersensitivity by different mechanisms (37.18)

Abstract

Allergen induced contact hypersensitivity(CHS) in the skin has been considered to be mediated by CD4+ Th1 and CD8+ Tc1 cells that produce IFN-γ. Our recent studies have demonstrated that CD8+ IL-17 producing T cells (TIL-17) play important roles in the elicitation of CHS. Allergen sensitization induces the development of CD8+ Tc1 and TIL-17 cells that are distinct T cell subpopulations. Here we demonstrate that both CD8+ Tc1 and TIL-17 cells play a role in the elicitation of CHS. However, they mediate inflammatory reactions in the skin by different mechanisms. CHS was reduced but not abolished in mice that were defect in the receptor for IFN-γ (IFN-γR−/−) or IL-17 (IL-17R−/−) compared to wild type controls. Similar results were observed in the adoptive transfer of CHS in the gene knockout mice that were transferred with allergen primed wild type CD8+ T cells. However, neutralization of IL-17 in IFN-γR−/− or IFN-γ in IL-17R−/− recipient mice abrogated the response. It implicates that both IFN-γ and IL-17 signals are involved in the elicitation of CHS and are required for optimal responses. Immunohistochemical analysis indicated that the infiltration of Gr-1+ granulocytes and CD11b+ macrophages in the allergen challenged skin of IL-17R−/− mice was significantly reduced whereas it was slightly affected in IFN-γR−/− mice. Further analysis using real time RT-PCR showed different patterns of chemokines and inflammatory cytokines in the allergen challenged skin of IFN-γR−/− or IL-17R−/− mice. These data indicate that both CD8+ Tc1 and TIL-17 cells take part in the elicitation of CHS and that specific mechanisms orchestrate Tc1 and TIL-17 mediated inflammatory reactions in the skin. The result of current studies may provide new insights into therapeutic strategies for T cell mediated inflammatory disorders.