Leishmania antigens presented by GM-CSF-derived macrophages protect susceptible mice against challenge with Leishmania major

Leishmania major, a causative agent of leishmaniasis, in humans is also capable of infecting mice. Several strains of mice, including the BALB/c strain, are unable to mount appropriate T cell responses to the parasite and develop a fatal, disseminated infection. We present evidence that injection of granulocyte-macrophage-CSF derived bone marrow macrophages (GMM phi), previously incubated with L. major antigens, into BALB/c mice before infection, induced a Th1-dominated response and subsequent healing. Injection of BALB/c mice with GMM phi pulsed with irrelevant Ag, or other macrophages pulsed with L. major Ag, failed to protect against L. major challenge. Protection induced by L. major Ag-bearing GMM phi correlated with the induction of a Th1-like response with the production of high levels of IFN-gamma, delayed-type hypersensitivity reactivity and long-lived resistance to reinfection. GMM phi-T cell interaction, rather than parasite killing by GMM phi, appeared to be a crucial step and there was a strong correlation between ability to function as APC in vitro and induction of protective immunity in vivo. These data suggest that presentation of Ag by a population of L. major Ag-bearing GMM phi can activate Th1 cells in BALB/c mice, leading to a protective immune response to parasite invasion. This implies that the nature of the APC population which presents Ag may influence the response to that Ag in vivo.