Interleukin-12 stimulation of lymphoproliferative responses in Trypanosoma cruzi infection.
The cytokine interleukin-12 (IL-12) is essential for resistance to Trypanosoma cruzi infection because it stimulates the synthesis of interferon-gamma (IFN-gamma), a major activator of the parasiticidal effect of macrophages. A less studied property of IL-12 is its ability to amplify the proliferation of T or natural killer (NK) lymphocytes. We investigated the role of endogenously produced IL-12 in the maintenance of parasite antigen (T-Ag)-specific lymphoproliferative responses during the acute phase of T. cruzi infection. We also studied whether treatment with recombinant IL-12 (rIL-12) would stimulate T-Ag-specific or concanavalin A (Con A)-stimulated lymphoproliferation and abrogate the suppression that is characteristic of the acute phase of infection. Production of IL-12 by spleen-cell cultures during T. cruzi infection increased in the first days of infection (days 3-5) and decreased as infection progressed beyond day 7. The growth-promoting activity of endogenous IL-12 on T-Ag-specific proliferation was observed on day 5 of infection. Treatment of cultures with rIL-12 promoted a significant increase in Con A-stimulated proliferation by spleen cells from normal or infected mice. Enhanced T-Ag-specific proliferation by rIL-12 was seen in spleen cell cultures from infected mice providing that nitric oxide production was inhibited by treatment with the competitive inhibitor NG-monomethyl-L-arginine (NMMA). Enhancement of proliferation promoted by IL-12 occurred in the presence of neutralizing anti-interleukin-2 (IL-2) antibody, suggesting that this activity of IL-12 was partly independent of endogenous IL-2. Thymidine incorporation levels achieved with rIL-12 treatment of the cultures were approximately 50% of those stimulated by rIL-2 in the same cultures.
Galvão da Silva
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AP
Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil.
de Almeida Abrahamsohn
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D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D018929:Cell Culture Techniques; D002455:Cell Division / Q000276:immunology; D014355:Chagas Disease / Q000276:immunology*; D003208:Concanavalin A / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D007376:Interleukin-2; D011994:Recombinant Proteins; D003208:Concanavalin A; D018664:Interleukin-12