The surface protein superfamily of Trypanosoma cruzi stimulates a polarized Th1 response that becomes anergic.
Trypanosoma cruzi is an obligate intracellular parasite that chronically infects mammals. Extracellular mammalian stage trypomastigotes simultaneously express and release multiple members of the parasite's surface protein superfamily; these extracellular proteins should stimulate MHC class II-restricted CD4 T cells. The surface protein superfamily, however, encodes variant epitopes that may inhibit this CD4 response. In this report the surface protein-specific CD4 response was investigated. CD4 cells isolated from acutely and chronically infected mice did not proliferate when stimulated with surface proteins. Adoptive transfer of surface protein-specific CD4 clones or immunization with a peptide encoding a surface protein T cell epitope protected mice during T. cruzi infection. These data strongly suggested that surface proteins were expressed and presented to CD4 cells during infection. Limiting dilution analysis identified an expanded population of surface protein-specific CD4 cells during the acute and chronic infection. These surface protein-specific CD4 cells did not produce IL-2 or IL-4, but did produce IFN-gamma. Enzyme-linked immunospot analyses confirmed that many of the surface protein-specific CD4 cells produce IFN-gamma. Together these results suggest that during T. cruzi infection a potentially protective CD4 response becomes anergic. It is possible that this anergy is induced by variant T cell epitopes encoded by the surface protein superfamily.
Millar
A E
AE
Department of Pediatrics and Pathobiology, University of Washington, Seattle, WA 98195, USA.
Wleklinski-Lee
M
M
Kahn
S J
SJ
D019264:Adoptive Transfer; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D014355:Chagas Disease; D017635:Clonal Anergy; D007371:Interferon-gamma / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015800:Protozoan Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*
D000953:Antigens, Protozoan; D000954:Antigens, Surface; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; C096427:SA85 1.1 antigen, Trypanosoma cruzi; D007371:Interferon-gamma