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01 August 2004

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

Fabíola Cardillo, Auro Nomizo, Edilberto Postol, José Mengel

Med Sci Monit 2004; 10(8): BR259-267 :: ID: 11729

Abstract

Background:This study evaluated the regulatory function of NK1.1+ cells during Trypanosoma cruzi 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 in vivo 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 T. cruzi 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-tre­ated 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 T. cruzi infection. Without NK1.1 cells, T lymphocytes are hyperactivated but do not differentiate to effector/memory T cells in infected C57Bl/6 mice.

Keywords: Antigens, CD - metabolism, Antigens, CD44 - metabolism, Antigens, Differentiation, T-Lymphocyte - metabolism, Interferon Type II - metabolism, Interleukin-2 - metabolism, Killer Cells, Natural - immunology, Mice, Inbred C57BL, Nitric Oxide - metabolism, Spleen - immunology, Spleen - parasitology, T-Lymphocytes - immunology, Trypanosoma cruzi - immunology, Antigens, CD - metabolism, Antigens, CD44 - metabolism, Antigens, Differentiation, T-Lymphocyte - metabolism, Interferon-gamma - metabolism, Interleukin-2 - metabolism, Killer Cells, Natural - immunology, Lectins, C-Type, Mice, Inbred C57BL, Nitric Oxide - metabolism, Spleen - parasitology, T-Lymphocytes - immunology, Trypanosoma cruzi - immunology

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750