Differential effects of Trypanosoma cruzi on the transcription of the p55IL-2R, c-fos, c-myc and CD69 genes in activated human lymphocytes.

Mitogen-activated lymphocytes co-cultured with either purified Trypanosoma cruzi trypomastigotes or the filtrate of trypomastigote suspensions in culture medium manifest a significant decrease in their capacities to express p55 interleukin-2 receptor molecules (p55IL-2R) on their membrane and proliferate. In this study we found that the cytoplasmic levels of p55IL-2R are also markedly reduced under these conditions. This inhibition appeared to result from altered gene transcription since the levels of p55IL-2R mRNA in phytohaemagglutinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMC) dropped substantially in the presence of parasite suspension filtrate. The rates of decay for p55IL-2R mRNA determined in cultures lacking and containing the parasite filtrate after addition of actinomycin D to inhibit further RNA synthesis were comparable. These results indicated that decreased p55IL-2R mRNA was not due to decreased stability of this mRNA under our conditions and pointed to a transcriptional or pre-transcriptional modification as the likely mechanism by which T. cruzi affects activated lymphocytes. The parasite filtrate did not appear to affect transcription of c-fos or c-myc (known to occur in the very early stages of lymphocyte activation) or that of CD69 (which is concomitant with p55IL-2R transcription). Thus, decreased p55IL-2R gene transcription appears to be a somewhat selective effect of a T. cruzi-derived molecule(s) rather than the consequence of an overall shutdown of gene transcription.