The Central Memory CD4⁺ T Cell Population Generated during Leishmania major Infection Requires IL-12 to Produce IFN-γ

Abstract

Central memory CD4⁺ T cells provide a pool of lymph node-homing, Ag-experienced cells that are capable of responding rapidly after a secondary infection. We have previously described a population of central memory CD4⁺ T cells in Leishmania major-infected mice that were capable of mediating immunity to a secondary infection. In this study, we show that the Leishmania-specific central memory CD4⁺ T cells require IL-12 to produce IFN-γ, demonstrating that this population needs additional signals to develop into Th1 cells. In contrast, effector cells isolated from immune mice produced IFN-γ in vitro or in vivo in the absence of IL-12. In addition, we found that when central memory CD4⁺ T cells were adoptively transferred into IL-12-deficient hosts, many of the cells became IL-4 producers. These studies indicate that the central memory CD4⁺ T cell population generated during L. major infection is capable of developing into either Th1 or Th2 effectors. Thus, continued IL-12 production may be required to ensure the development of Th1 cells from this central memory T cell pool, a finding that has direct relevance to the design of vaccines dependent upon central memory CD4⁺ T cells.