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 plasmid DNA containing the gene encoding for the catalytic domain of trans-sialidase, an important enzyme expressed on the surface of Trypanosoma cruzi trypomastigotes. These clones allowed us to study in vitro the interaction between T cells and T. cruzi-infected macrophages. A cytotoxic CD4 clone of the Th1 type effectively activated macrophages to kill intracellular amastigote forms of T. cruzi. In contrast, CD4 Th2-like clones were much less efficient, being unable to activate macrophages to significantly reduce parasite 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 the anti-parasitic activity of these cells. We conclude that trypomastigote-specific Th1 cells activate macrophages to kill intracellular amastigotes of T. cruzi by a mechanism exclusively dependent on the induction of nitric oxide synthesis.
Rodrigues
M M
MM
Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina, Rua Botucatu 862 6A, São Paulo, SP 04023-062, Brazil. rodriguesm@ecb.epm.br
Ribeirão
M
M
Boscardin
S B
SB
D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009439:Neuraminidase / Q000235:genetics / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000276:immunology*
D000953:Antigens, Protozoan; D016207:Cytokines; D006023:Glycoproteins; D009569:Nitric Oxide; D007371:Interferon-gamma; C069715:trans-sialidase; D009439:Neuraminidase