Cell-mediated cytotoxicity to Trypanosoma cruzi: I. Antibody-dependent cell mediated cytotoxicity to trypomastigote bloodstream forms

Abstract

The antibody-dependent, cell-mediated cytotoxicity (ADCC) to trypomastigote blood-stream forms of Trypanosoma cruzi was examined, utilizing trypanosomes isolated from mice infected with “Y” and “CL” stocks, normal mouse spleen (NMSC), or peritoneal (NMPC) cells and homologous immune serum (IMS). The incubations were performed at 35°C for 18 hr and the cytotoxicity was expressed as the percentage reduction in the number of motile trypanosomes. At an effector-target ratio of 40:1, NMSC induced a significant reduction in the number of motile trypanosomes of both “Y” and “CL” stocks. With trypanosomes obtained from nonirradiated mice this effect was frequently observed even in absence of IMS in the incubation mixture. In contrast, with trypanosomes obtained from irradiated mice, the presence of IMS was a prerequisite for the reaction. The loss in the motility of trypanosomes correlates well with their capacity to infect C3H/He mice, a strain that is highly susceptible to T. cruzi infection. ADCC to trypanosomes was also detected when NMPC were used, and the cytotoxic cells were found only in the nonadherent cell population. A striking difference was observed when immune mouse spleen cells (IMSC) were substituted for normal spleen cells: IMSC were only able to mediate cytotoxicity against trypanosomes raised in irradiated mice, an effect blocked by the simultaneous presence of IMS in the incubation mixture. It appears, therefore, that in infected mice the cells endowed with the capacity to mediate ADCC are blocked and that the immune cytotoxic cells are ineffective when the parasites are covered with specific antibodies.