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.
Doherty
T M
TM
Department of Immunology, DNAX Research Institute for Cellular and Molecular Biology, Palo Alto, CA 94304.
Coffman
R L
RL
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D000953:Antigens, Protozoan / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D015847:Interleukin-4 / Q000096:biosynthesis; D007895:Leishmania tropica / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000953:Antigens, Protozoan; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor