Abstract
Infection with the intracellular protozoan parasite Leishmania major induces a state of concomitant immunity wherein secondary immunity is dependent upon the persistence of the original pathogen. Our laboratory has described two populations of Leishmania-induced CD4(+) T cells that contribute to immunity: CD62L(high) central memory T (T(CM)) cells and CD62L(low) effector T cells. To determine whether the prosurvival cytokine IL-7 contributes to maintaining these T cells, we examined expression of the IL7R on CD4(+) T cells activated during L. major infection. We found that T(CM) cells present in chronically infected mice expressed high levels of the IL7R. However, in addition to the expression of the IL7R by T(CM) cells, CD62L(low) cells responding to L. major infection expressed the IL7R. Additional experiments revealed that a large percentage of the IL7R(high)CD62L(low) cells were Th1 cells, based on transcription at the IFN-gamma locus and up-regulation of the Th1-promoting transcription factor T-bet. The up-regulation 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 decreased the number of T-bet(+)CD4(+) T cells, reduced IFN-gamma production, and inhibited delayed-type hypersensitivity responses in immune mice challenged with L. major, indicating that IL7R signaling contributes to the maintenance of Th1 effector cells. Thus, both T(CM) and Th1 effector cells can express the IL7R during chronic L. major infection, which provides a potential means for their long-term survival in addition to the presence of persisting parasites.