TRYPANOSOMA-CRUZI DOWN-REGULATES THE PRODUCTION OF INTERLEUKIN-2, INTERFERON-GAMMA, INTERLEUKIN-4 AND INTERLEUKIN-5 BY ACTIVATED HUMAN-LYMPHOCYTES

The intracellular levels of interleukin (IL)-2, IL-4, IL-5 and interfe ron-gamma (IFN-gamma) produced by mitogen-stimulated normal human bloo d lymphocytes were found to be markedly reduced in cultures containing purified Trypanosoma cruzi trypomastigotes. This was evidenced by mar ked decreases in the proportion of lymphocytes whose cytoplasm was sta ined with fluorochrome-conjugated monoclonal antibodies specific for t he selected cytokines and a somewhat small but systematically demonstr able reduction in the mean fluorescence intensity of the stained lymph ocytes relative to values obtained with parasite-free cultures. The pe rcentage of activated CD3(+) cells containing both IL-2, IL-4, i.e., T HO-like cells, was also much smaller in the cultures containing trypom astigotes, indicating that T. cruzi can concomitantly inhibit the prod uction of more than 1 cytokine by individual activated T lymphocytes. These results evidence the ability of T. cruzi to down-regulate the pr oduction of several important cytokines and raise the possibility of a direct role for this parasite in altering cytokine production during infection.