title: Defective vaccine-induced immunity to Schistosoma mansoni in P strain mice. II. Analysis of cellular responses.
abstract: Cellular immune responses against larval and adult schistosome antigens were studied in attenuated cercariae-vaccinated P and C57BL/6 mice to define differences correlating with the inability of P mice to develop vaccine-induced resistance to challenge Schistosoma mansoni infection. Vaccinated P mice failed to demonstrate delayed hypersensitivity upon skin-testing with soluble worm antigens, whereas mice of the highly resistant strain C57BL/6 developed a significant 24-hr response to worm antigens in vivo. Also, when schistosome antigens were injected i.p., vaccinated P mice failed to exhibit an activated macrophage response in vivo, whereas vaccinated C57BL/6 mice developed macrophages with significant larvicidal and tumoricidal activity at the site of specific antigen challenge. Immune sera from either vaccinated C57BL/6 or P mice were equally effective at opsonizing the schistosomula targets in the larvicidal assay. In vitro analyses of cellular defects revealed that although T lymphocytes from vaccinated P mice showed blastogenic responses to schistosome antigens that were similar in magnitude and kinetics to those of cells from the C57BL/6 animals, T cells from C57BL/6 mice produced higher levels of macrophage-activating lymphokines (LK), including gamma-interferon. Macrophages from control C57BL/6 mice were also more responsive to activation by LK than macrophages from P mice were, as assessed by stimulation of these cells to kill skin-stage schistosomula in vitro. These two aspects of cellular dysfunction in P mice had the combined effect of rendering P macrophages incapable of activation by LK from mice of their own strain, whereas macrophages from C57BL/6 mice were strongly activated by LK from vaccinated C57BL/6 mice in the same assays. Thus, a correlation exists between T lymphocyte/macrophage dysfunction and lack of resistance to challenge infection in vaccinated P mice, which suggests that delayed hypersensitivity response plays a major role in the immunity to S. mansoni infection that is induced by exposure to radiation-attenuated cercariae.
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D005260:Female; D006969:Hypersensitivity, Immediate / Q000276:immunology; D007106:Immune Sera / Q000494:pharmacology; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000378:metabolism; D007814:Larva / Q000276:immunology; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains / Q000276:immunology*; D012550:Schistosoma mansoni / Q000254:growth & development / Q000276:immunology*; D013154:Spleen / Q000378:metabolism; D014612:Vaccines / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D000941:Antigens; D007106:Immune Sera; D008222:Lymphokines; D014612:Vaccines; D007371:Interferon-gamma