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

Abstract

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-06-18T12:17:42Z No. of bitstreams: 1 Cardillo F NK! 1 are required....pdf: 1290378 bytes, checksum: 13c8e37095d5f8e755e95fbabbf02a6b (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-06-18T13:03:27Z (GMT) No. of bitstreams: 1 Cardillo F NK! 1 are required....pdf: 1290378 bytes, checksum: 13c8e37095d5f8e755e95fbabbf02a6b (MD5)Made available in DSpace on 2015-06-18T13:03:27Z (GMT). No. of bitstreams: 1 Cardillo F NK! 1 are required....pdf: 1290378 bytes, checksum: 13c8e37095d5f8e755e95fbabbf02a6b (MD5) Previous issue date: 2004University of São Paulo. Institute for Biomedical Sciences IV. Department of Immunology. São Paulo, SP, Brasil / University of São Paulo. Department of Clinical Analysis. São Paulo, SP, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Doença Experimental de Chagas, Imunologia Celular e Auto-imunidade. Salvador, BA, BrasilUniversity of São Paulo. Department of Clinical Analysis. São Paulo, SP, BrasilUniversity of São Paulo. Institute for Biomedical Sciences IV. Department of Immunology. São Paulo, SP, BrasilUniversity of São Paulo. Institute for Biomedical Sciences IV. Department of Immunology. São Paulo, SP, Brasil / University of São Paulo. Department of Clinical Analysis. São Paulo, SP, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Doença Experimental de Chagas, Imunologia Celular e Auto-imunidade. Salvador, BA, BrasilBACKGROUND: 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+ 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+ CD44high 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+ 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