Trypanosoma cruzi inhibits the expression of CD3, CD4, CD8, and IL-2R by mitogen-activated helper and cytotoxic human lymphocytes

Abstract

We studied the effects of Trypanosoma cruzi secretion products on the capacity of helper (Th) and cytotoxic (Tc) cells to express IL-2R, CD3, CD4, and CD8 in response to PHA or anti-CD3 stimulation. To this end, we used a culture system in which blood forms of the parasite were cocultured with human PBMC. Two-color flow cytometry studies revealed that, under these conditions, there was a significant decrease in the percentage of both Th and Tc cells expressing IL-2R (inhibition range = 30 to 65%). These effects were already demonstrable 18 h after mitogenic activation, and maximal reductions occurred after 48-72 h. T cruzi-induced suppression of IL-2R expression was accompanied by a marked decrease in surface CD3, CD4, and CD8. The surface densities of these markers on the CD3+, CD4+, and CD8+ cells was markedly inhibited by the parasite. This effect was sometimes accompanied by a significant drop in the percentage of positive cells. Diminished expression of all of these surface molecules was observed on activated, but not on resting cells, i.e., no effects occurred in the absence of mitogen. The suppressed expression of CD3, CD4, and CD8 was also seen at 18 h, and occurred concomitantly with a marked decrease in cell proliferation. The inhibited expression of IL-2R, CD3, CD4, and CD8 molecules by Th and Tc might underlie the immunosuppression that occurs during the acute phase of Chagas disease (caused by T. cruzi). Our recent observation that the parasite suppresses responses of human lymphocytes separated by a cell-impermeable membrane, raises hopes that parasite product(s) may be useful reagents for studying the regulation of the expression of IL-2R, CD3, CD4, and CD8, which are known to play key roles during lymphocyte activation.