Interleukin-7 receptor (IL7R) expression provides the potential for long-term survival of both CD62Lhigh central memory T cells and Th1 effector cells during Leishmania major infection (96.6)

Abstract

Abstract Infection with the protozoan parasite Leishmania major induces a state of concomitant immunity wherein secondary immunity is dependent upon the persistence of the original pathogen. Our lab has described two populations of L. major-induced CD4+ T cells that contribute to immunity: CD62Lhigh central memory T (TCM) cells and CD62Llow effector T (TEFF) cells. To determine if the prosurvival cytokine interleukin-7 (IL-7) contributes to maintaining these T cells, we examined IL-7 receptor (IL7R) expression on CD4+ T cells activated during L. major infection. We found that TCM cells present in chronically infected mice expressed high levels of the IL7R. However, we also found that CD62Llow cells responding to L. major infection expressed the IL7R. A large percentage of the IL7Rhigh CD62Llow cells were Th1 cells, based on transcription at the IFN-γ locus and upregulation of the Th1 transcription factor T-bet. The upregulation of T-bet did not prevent IL7R expression by L. major-responding CD4+ T cells nor did the absence of T-bet result in increased IL7R expression. Finally, blockade of IL7R signaling inhibited delayed type hypersensitivity responses in immune mice challenged with L. major, indicating that IL7R signaling contributes to the maintenance of Teff cells. Thus, both TCM and Th1 effector cells can express the IL7R during chronic L. major infection, which provides a potential means for their long-term survival.