NK1.1 cells are required to control T cell hyperactivity during Trypanosoma cruzi infection

摘要

Background:This study evaluated the regulatory function of NK1.1+ cells during [i]Trypanosoma cruzi[/i] infection.Material/Methods: Both thymectomized (Tx C57Bl/6) and euthymic C57Bl/6 mice (C57Bl/6) were infected intraperitoneally with the Tulahuen strain. NK1.1[sup]+[/sup] cells were depleted [i]in vivo[/i] by anti-NK1.1 mAb. Spleen cells were analyzed by flow cytometry for the expression of CD44 and CD69 on T cells. Supernatants from splenocytes were used to measure nitrite concentration (quantified by Griess reagent). Interleukin 2 and IFN-gamma levels were determined by ELISA. The protocols used herein were approved by the Institutional Committee for Ethics. Student’s t or Kruskal-Wallis tests were applied, as indicated.Results: The number of T cells expressing CD69 increased progressively during [i]T. cruzi[/i] infection in NK1.1 cell-depleted C57Bl/6 mice. In spite of an increased early T cell activation during infection, the percentage of CD4[sup]+[/sup] CD44[sup]high[/sup] T cells did not augment in NK1.1 cell-depleted C57Bl/6 mice compared with untreated C57Bl/6 controls. Serum levels of IFN-gamma in anti-NK1.1-treated mice were higher than in non-depleted animals. Con-A-stimulated spleen cell supernatants from NK1.1 cell-depleted animals contained increased levels of IL-2 and nitric oxide (NO) during early infection.Conclusions: After the first week of infection, NO overproduction and high levels of IFN-gamma in anti-NK1.1-tre-ated C57Bl/6 mice appeared to be related to susceptibility and hyperactivation of peripheral T cells. Finally, this study suggests a novel regulatory function of NK1.1[sup]+[/sup] cells during [i]T. cruzi[/i] infection. Without NK1.1 cells, T lymphocytes are hyperactivated but do not differentiate to effector/memory T cells in infected C57Bl/6 mice.