Deletion of IL-4Ralpha on CD4 T cells renders BALB/c mice resistant to Leishmania major infection.

Deletion of IL-4Ralpha on CD4 T cells renders BALB/c mice resistant to Leishmania major infection.

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Effector responses induced by polarized CD4+ T helper 2 (Th2) Lid Switch cells drive nonhealing responses in BALB/c mice infected with Leishmania major.Th2 cytokines IL-4 and IL-13 are known susceptibility factors for L.major infection in BALB/c mice and induce their biological functions through a common receptor, the IL-4 receptor alpha chain (IL-4Ralpha).IL-4Ralpha-deficient BALB/c mice, however, remain susceptible to L.major infection, indicating that IL-4/IL-13 may induce protective responses.

Therefore, the roles of polarized Th2 CD4+ T cells and IL-4/IL-13 responsiveness of non-CD4+ T cells in inducing non-healer or healer responses have yet to be elucidated.CD4+ T cell-specific IL-4Ralpha (Lck(cre)IL-4Ralpha(-/lox)) deficient BALB/c mice were generated and characterized to elucidate the importance of IL-4Ralpha signaling during cutaneous leishmaniasis in the absence of IL-4-responsive CD4+ T cells.Efficient deletion was confirmed by loss of IL-4Ralpha expression on CD4+ T cells and impaired IL-4-induced CD4+ T cell proliferation and Th2 differentiation.CD8+, gammadelta+, and NK-T cells expressed residual IL-4Ralpha, and representative non-T cell populations maintained IL-4/IL-13 responsiveness.In contrast to IL-4Ralpha(-/lox) BALB/c mice, which developed ulcerating lesions following infection with L.

major, Lck(cre)IL-4Ralpha(-/lox) mice were resistant and showed protection to rechallenge, similar to healer C57BL/6 mice.Resistance to L.major in Lck(cre)IL-4Ralpha(-/lox) mice correlated with reduced numbers of IL-10-secreting cells and early IL-12p35 mRNA induction, leading to increased delayed type hypersensitivity responses, interferon-gamma production, and elevated ratios of inducible nitric oxide synthase mRNA/parasite, similar to C57BL/6 mice.These data demonstrate that abrogation of IL-4 signaling in VITAMIN D3 1000IU CD4+ T cells is required to transform non-healer BALB/c mice to a healer phenotype.Furthermore, a beneficial role for IL-4Ralpha signaling in L.

major infection is revealed in which IL-4/IL-13-responsive non-CD4+ T cells induce protective responses.