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IL-7 Receptor Expression Provides the Potential for Long-Term Survival of Both CD62L^high Central Memory T Cells and Th1 Effector Cells during Leishmania major Infection¹

Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104

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^highCD62L^low cells were Th1 cells, based on transcription at the IFN- 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- 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grant AI35914 (to P.S.).

² Address correspondence and reprint requests to Dr. Phillip Scott, Department of Pathobiology, School of Veterinary Medicine, Room 310 Hill Pavilion, 380 South University Avenue, Philadelphia, PA 19104-4539. E-mail address: pscott{at}vet.upenn.edu

³ Abbreviations used in this paper: T_EFF, effector T; T_CM, central memory T; DTH, delayed-type hypersensitivity; eYFP, enhanced yellow fluorescence protein; FTAg, freeze-thawed Ag; LN, lymph node; dLN, draining lymph node; pi, postinfection; WT, wild type; KO, knockout; dhfr-ts, dihydrofolate reductase-thymidylate synthase.