CD4 Th1 but not Th2 clones efficiently activate macrophages to eliminate Trypanosoma cruzi through a nitric oxide dependent mechanism

We have recently generated CD4 clones from BALB/c mice immunized with a pla smid DNA containing the gene encoding for the catalytic domain of trans-sia lidase, an important enzyme expressed on the surface of Trypanosoma cruzi t rypomastigotes. These clones allowed us to study in vitro the interaction b etween T cells and T. cruzi-infected macrophages. A cytotoxic CD4 clone of the Th1 type effectively activated macrophages to kill intracellular amasti gote forms of T. cruzi. In contrast, CD4 Th2-like clones were much less eff icient, being unable to activate macrophages to significantly reduce parasi te development. We found that the anti-parasitic activity of Th1 cells was completely suppressed by the presence of nitric oxide synthase inhibitors. Also, we observed that anti-IFN-gamma antibodies significantly inhibited th e anti-parasitic activity of these cells. We conclude that trypomastigote-s pecific Th1 cells activate macrophages to kill intracellular amastigotes of T. cruzi by a mechanism exclusively dependent on the induction of nitric o xide synthesis. (C) 2000 Elsevier Science B.V. All rights reserved.