title: Trypanosoma musculi: characterization of the T-lymphocyte dependency of immunity by selective immunomodulation of the mouse, Mus musculus.
abstract: Trypanosoma musculi is a hemoflagellate parasite producing a characteristic course of infection in the mouse, terminating in elimination of the parasite from the vascular system with permanent immunity to reinfection. While this elimination is known to require functional T lymphocytes, the role of these cells has remained undefined. The current study examined the role of T-lymphocyte dependency by the selective in vivo depletion of T-lymphocyte subsets by monoclonal antibodies or immunosuppressive pharmacologic agents. In the former approach, monoclonal antibodies specific for the murine T-lymphocyte surface antigens Thy 1.2, Lyt 2, or L3T4 were administered to mice, resulting in functional depletion of either all T lymphocytes or the T-helper or T-cytotoxic subsets. Subsequent infection with T. musculi revealed that elimination of the T-helper, but not the T-cytotoxic, phenotype resulted in a prolonged and elevated parasitemia. This enhancement of parasitemia was similar to that produced with depletion of all T lymphocytes (i.e., Thy 1.2+ cells), suggesting that the T-helper cell was most important in parasite elimination. In the latter approach, pharmacologic agents displaying selective immunosuppressive activity were employed to inactivate, rather than destroy, T-lymphocyte subpopulations. In vivo inactivation of T-helper lymphocytes by the fungal metabolite cyclosporin-A enhanced the level of parasitemia in treated animals and resulted in a protracted duration of infection. In contrast, treatment with the highly substituted anthracenedione AEAD, which has been demonstrated to selectively inactivate T-cytotoxic cells, had no appreciable effect on the kinetics of infection. These results strongly suggest that the T-lymphocyte dependency of Trypanosoma musculi elimination is due predominantly to the action of the T-helper, rather than T-cytotoxic, lymphocyte.
authors.affiliation: Department of Cellular and Molecular Toxicology, Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709.
authors.forename: R V
authors.initials: RV
authors.lastname: House
authors.forename: J H
authors.initials: JH
authors.lastname: Dean
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D003524:Cyclosporins / Q000494:pharmacology; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000502:physiology; D007700:Kinetics; D051379:Mice; D008942:Mitoxantrone / Q000031:analogs & derivatives / Q000494:pharmacology; D013601:T-Lymphocytes / Q000145:classification / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology; D014352:Trypanosomiasis / Q000276:immunology*
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D003524:Cyclosporins; D007166:Immunosuppressive Agents; C043485:CL 232468; D008942:Mitoxantrone