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Contribution of NK, NK T, [gamma][delta] T, and [alpha]{szligbeta} T Cells to the Gamma Interferon Response Required for Liver Protection against Trypanosoma cruzi

Sardinha, Luiz Roberto, Elias, Rosa Maria, Mosca, Tainá, Bastos, Karina R. B., Marinho, Cláudio R. F., D'Império Lima, Maria Regina, Álvarez, José M.
Infection and immunity 2006 v.74 no.4 pp. 2031-2042
T-lymphocytes, Trypanosoma cruzi, amastigotes, immunity, inflammation, integrins, interferon-gamma, liver, mice, natural killer cells, parasites
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 {szligbeta}1 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{szligbeta}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]{szligbeta} (TCR[alpha]{szligbeta}), 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.