title: Human infection with Trypanosoma cruzi induces parasite antigen-specific cytotoxic T lymphocyte responses.
abstract: Experimental models of Chagas' disease, an infection caused by the intracellular protozoan Trypanosoma cruzi, have demonstrated the crucial immunoprotective role played by CD8(+) T lymphocytes. These cells dominate inflammatory foci in parasitized tissues and their elimination from mice leads to uncontrolled parasite replication and subsequent death of the infected host. A trypomastigote surface antigen, TSA-1, and two amastigote surface molecules, ASP-1 and ASP-2, were recently identified as targets of CD8(+) cytotoxic T lymphocytes (CTL) in T. cruzi-infected mice. Until now, however, there was no evidence for the development of parasite-specific CTL in T. cruzi-infected humans. In this study, human CTL specific for TSA-1-, ASP-1-, and ASP-2-derived peptides were detected in the peripheral blood mononuclear cells from 21 of 24 HLA-A2(+) T. cruzi-infected patients. CTL recognition was antigen specific, A2-restricted, and CD8(+) T cell-dependent. Demonstration of human CTL against T. cruzi and against target molecules identified using the murine model provides important information for the optimal design and evaluation of vaccines to prevent or ameliorate Chagas' disease.
authors.affiliation: Department of Cellular Biology, University of Georgia, Athens, Georgia 30602, USA.
authors.forename: B
authors.initials: B
authors.lastname: Wizel
authors.forename: M
authors.initials: M
authors.lastname: Palmieri
authors.forename: C
authors.initials: C
authors.lastname: Mendoza
authors.forename: B
authors.initials: B
authors.lastname: Arana
authors.forename: J
authors.initials: J
authors.lastname: Sidney
authors.forename: A
authors.initials: A
authors.lastname: Sette
authors.forename: R
authors.initials: R
authors.lastname: Tarleton
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D014355:Chagas Disease / Q000276:immunology / Q000469:parasitology; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007114:Immunization; D008565:Membrane Proteins / Q000276:immunology; D009439:Neuraminidase / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*; D014643:Variant Surface Glycoproteins, Trypanosoma
chemical_list: D000953:Antigens, Protozoan; D000954:Antigens, Surface; D000939:Epitopes; D015789:HLA-A2 Antigen; D008565:Membrane Proteins; D010446:Peptide Fragments; D014643:Variant Surface Glycoproteins, Trypanosoma; C070842:trypomastigote specific surface antigen; C106989:amastigote surface protein-1; D009439:Neuraminidase