Contribution of NKNK T, gamma delta T, and alpha beta T cells to the gamma interferon response required for liver protection against Trypanosoma cruzi

Author(s)

Sardinha, Luiz Roberto ; Elias, Rosa Maria ; Mosca, Tainá ; Bastos, Karina R. B. ; Marinho, Cláudio R. F. ; Lima, Maria Regina D´Império ; Mosig, José Maria Alvarez ^[7]

• Document type: Journal article
• Source: Infection and Immunity; v. 74, n. 4, p. 2031-2042, Apr. 2006.
• Field of knowledge: Biological Sciences - Immunology

Abstract

In the present work, we show that intracellular Trypanosoma cruzi is rarely found in the livers of acutely infected mice, but inflammation is commonly observed. The presence of numerous intrahepatic amastigotes in infected gamma interferon (IFN-gamma)-deficient mice corroborates the notion that the liver is protected by an efficient local immunity. The contribution of different cell populations was suggested by data showing that CD4- and CD8-deficient mice were able to restrain liver parasite growth. Therefore, we have characterized the liver-infiltrating lymphocytes and determined the sources of IFN-gamma during acute T. cruzi infection. We observed that natural killer (NK) cells increased by day 7, while T and B cells increased by day 14. Among CD3(+) cells, CD4(+), CD8(+), and CD4(-) CD8(-) cell populations were greatly expanded. A large fraction of CD3(+) cells were positive for PanNK, a 01 integrin expressed by NK and NK T cells. However, these lymphocytes were not classic NK T cells because they did not express NK1.1 and showed no preferential usage of V beta 8. Otherwise, liver NK T (CD3(+) NK1.1(+)) cells were not increased in acutely infected mice. The majority of PanNK(+) CD4(+) and PanNK(+) CD8(+) cells expressed T-cell receptor alpha beta (TCR alpha beta), whereas PanNK(+) CD4(-) CD8(-) cells were positive for TCR gamma delta. In fact, gamma delta T cells showed the most remarkable increase (40- to 100-fold) among liver lymphocytes. Most importantly, intracellular analysis revealed high levels of IFN-gamma production at day 7 by NK cells and at day 14 by CD4(+), CD8(+), and CD4(-) CD8(-) TCR gamma delta(+) cells. We concluded that NK cells are a precocious source of IFN-gamma in the livers of acutely infected mice, and, as the disease progresses, conventional CD4(+) and CD8(+) T cells and gamma delta T cells, but not classic NK-T cells, may provide the IFN-gamma required for liver protection against T. cruzi. (AU)