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.