NK1.1 cells are required to control T cell hyperactivity during Trypanosoma cruzi infection.
BACKGROUND
This study evaluated the regulatory function of NK1.1+ cells during Trypanosoma cruzi infection.


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.
Department of Immunology, Institute for Biomedical Sciences IV, Department of Clinical Analysis, University of ao Paulo, Sau Paulo, Brazil. cardillo@cpqgm.fiocruz.br
Fabíola
F
Cardillo
Auro
A
Nomizo
Edilberto
E
Postól
José
J
Mengel
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D005434:Flow Cytometry; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D013154:Spleen / Q000276:immunology* / Q000469:parasitology; D013601:T-Lymphocytes / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018960:Hyaluronan Receptors; D007371:Interferon-gamma; D007376:Interleukin-2; D037181:Lectins, C-Type; D009569:Nitric Oxide; D000099192:CD69 Antigens