The Early Generation of a Heterogeneous CD4+ T Cell Response to Leishmania major

CD4(+) T cells are an essential component of both the primary and secondary immune response against the intracellular protozoan parasite Leishmania major. Our laboratory has previously shown that CD62L(high)IL-7R(high) central memory T (T-CM) cells mediate protective immunity following secondary challenge. To determine when T-CM cells develop, we examined the phenotype of Leishmania-specific CD4(+) T cells in the first 2 wk following infection. As expected, we identified a population of CD4(+) T cells present in the draining lymph node with the characteristics of effector T cells. However, in addition, a second population phenotypically resembling T-CM cells emerged coincident with the effector population. These T cells, expressing CD62L, CCR7, and IL-7R, failed to produce IFN-gamma, but had the capacity to give rise to IFN-gamma-producing effector cells. Our studies also demonstrated that the degree of proliferation and the timing of lymph node entry impact T-CM cell development. The early generation of T-CM cells following L. major infection indicates that T-CM cells may not only control secondary infections, but may also contribute to the control of the primary infection. The Journal of Immunology, 2010, 185: 2416-2423.