The overall goal of this project is to define the mechanisms of suppression of antibody responses during chronic Trypanosoma cruzi infections. Using recent information generated in our laboratories, experiments will be performed to define the cellular and molecular basis for the observed deficiency in interleukin 2 (IL2) in infected mice. In vitro co-culture and in vivo cell transfer experiments will be used to achieve these goals. Emphasis will be placed on using responses to non-parasite antigens to determine the mechanisms of immunosuppression, although parasite-specific responses will also be examined. Based on recent observations that T. cruzi extracts can also suppress immune responses, we will define the conditions under which this occurs and characterize the parasite molecule(s) involved.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI022726-02
Application #
3134245
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1985-09-01
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Seattle Biomedical Research Institute
Department
Type
DUNS #
City
Seattle
State
WA
Country
United States
Zip Code
98109
Skeiky, Y A; Guderian, J A; Benson, D R et al. (1995) A recombinant Leishmania antigen that stimulates human peripheral blood mononuclear cells to express a Th1-type cytokine profile and to produce interleukin 12. J Exp Med 181:1527-37
Skeiky, Y A; Benson, D R; Guderian, J A et al. (1995) Immune responses of leishmaniasis patients to heat shock proteins of Leishmania species and humans. Infect Immun 63:4105-14
Skeiky, Y A; Benson, D R; Elwasila, M et al. (1994) Antigens shared by Leishmania species and Trypanosoma cruzi: immunological comparison of the acidic ribosomal P0 proteins. Infect Immun 62:1643-51
Reed, S G; Brownell, C E; Russo, D M et al. (1994) IL-10 mediates susceptibility to Trypanosoma cruzi infection. J Immunol 153:3135-40
Piuvezam, M R; Russo, D M; Burns Jr, J M et al. (1993) Characterization of responses of normal human T cells to Trypanosoma cruzi antigens. J Immunol 150:916-24
Silva, J S; Barral-Netto, M; Reed, S G (1993) Aggravation of both Trypanosoma cruzi and murine leukemia virus by concomitant infections. Am J Trop Med Hyg 49:589-97
Skeiky, Y A; Benson, D R; Guderian, J A et al. (1993) Trypanosoma cruzi acidic ribosomal P protein gene family. Novel P proteins encoding unusual cross-reactive epitopes. J Immunol 151:5504-15
Arnholdt, A C; Piuvezam, M R; Russo, D M et al. (1993) Analysis and partial epitope mapping of human T cell responses to Trypanosoma cruzi cysteinyl proteinase. J Immunol 151:3171-9
Skeiky, Y A; Benson, D R; Parsons, M et al. (1992) Cloning and expression of Trypanosoma cruzi ribosomal protein P0 and epitope analysis of anti-P0 autoantibodies in Chagas' disease patients. J Exp Med 176:201-11
Silva, J S; Morrissey, P J; Grabstein, K H et al. (1992) Interleukin 10 and interferon gamma regulation of experimental Trypanosoma cruzi infection. J Exp Med 175:169-74

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