CYTOTOXICITY IN PATIENTS WITH DIFFERENT CLINICAL FORMS OF CHAGAS-DISEASE

There are few studies on cell-mediated cytotoxicity in human Chagas' d isease. In the present study, we evaluated peripheral blood mononuclea r cell (PBMC) cytotoxicity activity from chagasic patients with differ ent clinical forms of disease. To verify the cytotoxic response, we pe rformed cell lysis assays using Cr-51-labelled K562 cells as targets. Results are reported as lyric units (LU = number of cells required for 30% lysis) per million PBMC. Exposure of patients' PBMC to Trypanosom a cruzi antigen led to an increase in cytotoxic activity compared with unstimulated patient cells against K562. Asymptomatic cardiomyopathy patients had higher responses (37.8 +/- 5.0 LU/10(6) PBMC; mean +/- s. d.) than indeterminate (11.5 +/- 3.6 LU/10(6)) and symptomatic cardiom yopathy (7.8 +/- 2.5 LU/10(6)). Normal control PBMC stimulated with T. cruzi antigen had 4.36 +/- 1.31 LU/10(6) PBMC against K562. Addition of recombinant interferon-gamma (IFN-gamma) did not lead to significan t increase in cytotoxicity in any group of patients. On the other hand , recombinant human IL-12 significantly increased cytotoxic responses From symptomatic cardiomyopathy patients and normal controls who prese nted low levels of cytotoxicity induced by T. cruzi antigen. The combi ned use of IL-12 and a neutralizing anti-IFN-gamma antibody did not ch ange IL-12-induced cytotoxic responses, showing the direct role of thi s cytokine on natural killer (NK) cells. NK cells were the main cells responsible for the lysis of K562 target cells as evidenced by testing cell subsets following magnetic cell sorting. These data demonstrate that chagasic patients with different clinical Forms of disease have P BMC which respond to T. cruzi antigen with a cytotoxic response, and t his response is up-regulated by IL-12.