The magnitude of CD4⁺ T-cell activation rather than TCR diversity determines the outcome of Leishmania infection in mice

CD4⁺ T cells play a critical role in determining the disease outcome in murine cutaneous leishmaniasis, and selective usage of T-cell receptor (TCR) is implied in promoting Leishmania major infection. However, little information is available on TCR usage in Leishmania-specific, IFN-γ-producing CD4⁺ T cells. In this study, we investigated the TCR diversity and activation of CD4⁺ T cells in a nonhealing model associated with L. amazonensis (La) infection and a self-healing model associated with L. braziliensis (Lb) infection. While marked expansion in the absolute number of several subsets was observed in Lb-infected mice, the percentages of TCR Vβ⁺CD4⁺-cell subsets were comparable in draining LN- and lesion-derived T cells in two infection models. We found that multiple TCR Vβ CD4⁺T cells contributed collectively and comparably to IFN-γ production and that the overall levels of IFN-γ production positively correlated with the control of Lb infection. Moreover, pre-infection with Lb parasites provided cross-protection against secondary La infection, owing to an enhanced magnitude of T-cell activation and IFN-γ production. Collectively, this study suggests that the magnitude of CD4⁺ T-cell activation, rather than the TCR diversity, is the major determining factor for the outcome of Leishmania infection.