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 als o capable of infecting mice. Several strains of mice, including the BA LB/c strain, are unable to mount appropriate T cell responses to the p arasite and develop a fatal, disseminated infection. We present eviden ce that injection of granulocyte-macrophage-CSF derived bone marrow ma crophages (GMMPHI), previously incubated with L. major antigens, into BALB/c mice before infection, induced a Th1-dominated response and sub sequent healing. Injection of BALB/c mice with GMMPHI pulsed with irre levant Ag, or other macrophages pulsed with L. major Ag, failed to pro tect against L. major challenge. Protection induced by L. major Ag-bea ring GMMPHI correlated with the induction of a Th1-like response with the production of high levels of IFN-gamma, delayed-type hypersensitiv ity reactivity and long-lived resistance to reinfection. GMMPHI-T cell interaction, rather than parasite killing by GMMPHI, appeared to be a crucial step and there was a strong correlation between ability to fu nction as APC in vitro and induction of protective immunity in vivo. T hese data suggest that presentation of Ag by a population of L. major Ag-bearing GMMPHI 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 resp onse to that Ag in vivo.