Two modes of idiotypic stimulation of T lymphocytes from patients with Chagas' disease: correlations with clinical forms of infection.
Patients with chronic Trypanosoma cruzi infections have peripheral auto-anti-idiotype (Id) T cells that proliferate on exposure to immunoaffinity-purified antibodies against T. cruzi epimastigote antigens (EPI). The responses of some patients' (group 1) peripheral blood mononuclear cells (PBMC) to anti-EPI antibodies from sera of patients with the cardiac form of Chagas' disease (Id-C) were inhibited by chloroquine, but responses of other patients' (group 2) PBMC to Id-C were not inhibited. PBMC responses of both group-1 and -2 patients to anti-EPI antibodies from asymptomatic (indeterminate) patients (Id-I) were inhibited by chloroquine, as were their responses to the antigens in EPI. Most patients (69%) in group 1 had indeterminate Chagas' disease, and 100% of the patients in group 2 had severe, cardiac or digestive Chagas' disease. Both the direct (chloroquine-insensitive) and indirect (processed) modes of stimulation by anti-EPI antibodies required adherent cells. In group 2 (direct stimulation), this requirement was met by exogenous IL-1, and neither anti-HLA-DR,DP(DQ) monoclonal antibody (mAb) nor sodium azide inhibited T-cell proliferation. Indirect Id stimulation of group-1 cells by Id-I or Id-C, and group-2 cells by Id-I or EPI, was inhibited by anti-HLA-DR,DP(DQ) mAb or sodium azide, and exogenous IL-1 alone did not support this processed, MHC-mediated T-cell stimulation, but live adherent cells did. The mode of activation of auto-anti-Id T cells from patients with Chagas' disease depends on the clinical form of infection of both the cell donor and the donor of the stimulating anti-EPI antibodies.
Gazzinelli
R T
RT
Departamento da Bioquimica e Imunologia, Universidade Federal de Minas Gerais, Brazil.
Gazzinelli
G
G
Cançado
J R
JR
Cardoso
J E
JE
Brener
Z
Z
Colley
D G
DG
D000328:Adult; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000913:Antibodies, Protozoan / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D000953:Antigens, Protozoan / Q000494:pharmacology; D002598:Chagas Cardiomyopathy / Q000276:immunology*; D014355:Chagas Disease / Q000276:immunology*; D002738:Chloroquine / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008213:Lymphocyte Activation / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007376:Interleukin-2; D002738:Chloroquine