DIFFERENTIAL-EFFECTS OF TRYPANOSOMA-CRUZI ON THE TRANSCRIPTION OF THEP55IL-2R, C-FOS, C-MYC AND CD69 GENES IN ACTIVATED HUMAN-LYMPHOCYTES

Mitogen-activated lymphocytes co-cultured with either purified Trypano soma cruzi trypomastigotes or the filtrate of trypomastigote suspensio ns in culture medium manifest a significant decrease in their capaciti es 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 sin ce 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 f or p55IL-2R mRNA determined in cultures lacking and containing the par asite filtrate after addition of actinomycin D to inhibit further RNA synthesis were comparable. These results indicated that decreased p55I L-2R mRNA was not due to decreased stability of this mRNA under our co nditions and pointed to a transcriptional or pre-transcriptional modif ication as the likely mechanism by which T. cruzi affects activated ly mphocytes. The parasite filtrate did not appear to affect transcriptio n of c-fos or c-myc (known to occur in the very early stages of lympho cyte activation) or that of CD69 (which is concomitant with p55IL-2R t ranscription). Thus, decreased p55IL-2R gene transcription appears to be a somewhat selective effect of a T. cruzi-derived molecule(s) rathe r than the consequence of an overall shutdown of gene transcription.