NK1.1 cells are required to control T cell hyperactivity during Trypanosoma cruzi infection Fabíola Cardillo 1–3 ABCDEFG, Auro Nomizo 2 B, Edilberto Postól 1 B, José Mengel 1–3 ADFG 1 Department of Immunology, Institute for Biomedical Sciences IV, University of São Paulo. São Paulo, Brazil 2 Department of Clinical Analysis, University of São Paulo, São Paulo, Brazil 3 Oswaldo Cruz Foundation, Gonçalo Moniz Research Center, Bahia, Brazil. Cellular Immunology, Autoimmunity and Experimental Chagas’ Disease Laboratory, Brazil Source of support: This work was supported by FAPESP (proc. numbers FC 97/06225-0 and JM 95/09379-2) and by CNPq. F.C. and E.P. are recipients of research fellowships from FAPESP (respectively 97/10426 and 99/ 10621-3) and J.M. is the recipient of a research fellowship from CNPq, Brazil. Summary Background: This study evaluated the regulatory function of NK1.1 + cells during Trypanosoma cruzi infection. Matreial/Methods: Both thymectomized (Tx C57Bl/6) and euthymic C57Bl/6 mice (C57Bl/6) were infected intraperi- toneally 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 indica- ted. 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 + CD44 high T cells did not augment in NK1.1 cell-depleted C57Bl/6 mice com- pared 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 infec- tion. 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 infec- tion. Without NK1.1 cells, T lymphocytes are hyperactivated but do not differentiate to effector/ memory T cells in infected C57Bl/6 mice. key words: T. cruzi • NK1.1 T cells • regulatory cells • IFN-gamma • nitric oxide • Interleukin-2 Full-text PDF: http://www.MedSciMonit.com/pub/vol_10/no_8/4290.pdf Word count: 3698 Tables: 1 Figures: 6 References: 43 Author’s address: Dr. Fabíola Cardillo, Oswaldo Cruz Foundation, Centro de Pesquisas Gonçalo Moniz. R. Waldemar Falcão 121, CEP 40295-001. Salvador, Bahia, Brazil, e-mail: cardillo@cpqgm.fiocruz.br Authors’ Contribution: A Study Design B Data Collection C Statistical Analysis D Data Interpretation E Manuscript Preparation F Literature Search G Funds Collection Received: 2003.10.27 Accepted: 2004.05.26 Published: 2004.08.01 BR259 Basic Research WWW. MED S CI MONIT .COM © Med Sci Monit, 2004; 10(8): BR259-267 PMID: 15277986 BR