Increased natural cytotoxicity receptor expression and relevant IL‐10 production in NK cells from chronically infected viremic HCV patients

European Journal of Immunology - Tập 37 Số 2 - Trang 445-455 - 2007
Andrea De Maria1,2,3,4, Manuela Fogli1,3,5, Stefania Mazza6, Monica Basso3, A. Picciotto3, Paola Costa2,7, Sonia Congia2, Maria Cristina Mingari8,4, Lorenzo Moretta2,6,7
1Authors contributed equally to this work
2Center of Excellence for Biomedical Research, CEBR, University of Genova, Genova, Italy
3Department of Internal Medicine, University of Genova, Genova, Italy
4IST-GE, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
5NIAID, National Institutes of Health, Bethesda, Maryland, USA
6Department of Experimental Medicine, University of Genova, Genova, Italy
7Istituto Scientifico G. Gaslini, Genova, Italy
8Department of Oncology, Biology and Genetics, University of Genova, Genova, Italy

Tóm tắt

AbstractHepatitis C virus (HCV) readily establishes high‐level lifelong persistent infection in the majority of immunocompetent adults with failure of HCV‐specific CD8+ CTL to clear viral replication. Virus‐induced conditioning of innate immune responses is a possible mechanism that may contribute to the impairment of virus‐specific CD8+ CTL responses. Here, we analyzed whether triggering of NK cell receptor expression and function is affected during chronic viremic HCV infection. Flow cytometric analysis of purified resting peripheral NK cells showed no evidence of NK cell activation, while analysis of natural cytotoxicity receptors (NCR) showed that NK cells from HCV‐infected patients had selective increased expression of NKp30 and NKp46. NK cells had corresponding conserved cytotoxic activity against all targets with the exception of HepG2 hepatoma cells. Freshly separated NK cells from HCV patients showed significant production of IL‐10 and normal concentrations of IFN‐γ upon cell‐mediated triggering. Thus, increased expression of NKp30 during HCV infection with increased IL‐10 production could contribute, once NK cells localize in the liver, to a NK‐DC crosstalk leading to skewing of subsequent adaptive immune responses and lack of virus control.

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European Journal of Immunology

Tập 37 Số 2

445-455

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