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Interleukin‐12 stimulation of lymphoproliferative responses in Trypanosoma cruzi infection
Author(s) -
Galvão da Silva Ana Paula,
De Almeida Abrahamsohn Ises
Publication year - 2001
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2001.01311.x
Subject(s) - trypanosoma cruzi , biology , spleen , immunology , lymphoproliferative response , cytokine , interferon gamma , interleukin 2 , t cell , concanavalin a , immune system , in vitro , parasite hosting , peripheral blood mononuclear cell , biochemistry , world wide web , computer science
Summary The cytokine interleukin‐12 (IL‐12) is essential for resistance to Trypanosoma cruzi infection because it stimulates the synthesis of interferon‐γ (IFN‐γ), 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 N G ‐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 ≈ 50% of those stimulated by rIL‐2 in the same cultures.