title: Trypanosoma cruzi: roles for perforin-dependent and perforin-independent immune mechanisms in acute resistance.
abstract: CD8+ T cells have been shown to be required for acute resistance to infection with the protozoan parasite, Trypanosoma cruzi, the causative agent of Chagas' disease. However, to date, the mechanism by which CD8+ T cells mediate protection in vivo has not been determined. While CD8+ T cells can exhibit cytolytic function, they also secrete cytokines such as IFN-gamma, which is known to mediate protection against T. cruzi infections. To determine whether cytolysis is an important effector function in vivo, we have compared outcomes of T. cruzi infection in normal and perforin-deficient mice. Our results indicate that while perforin-dependent cytolytic mechanisms clearly make a major contribution to acute resistance to T. cruzi infection, this contribution may be strain and challenge dose-dependent, since perforin-deficient mice challenged with lower doses of a less virulent strain survived and were subsequently resistant to challenge with virulent organisms. In vivo depletion studies demonstrated that survival of perforin-deficient mice challenged with low doses of T. cruzi requires both CD4+ and CD8+ T cells and is dependent on IFN-gamma secretion. These studies document the participation of both perforin-dependent cytotoxic and perforin-independent, IFN-gamma-dependent immune mechanisms in acute resistance to T. cruzi infection.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, New Mexico, 87131, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Nickell
authors.forename: D
authors.initials: D
authors.lastname: Sharma
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D014355:Chagas Disease / Q000276:immunology* / Q000469:parasitology; D005260:Female; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018512:Parasitemia / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology* / Q000472:pathogenicity; D014774:Virulence
chemical_list: D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D007371:Interferon-gamma