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Natural killer cell activation enhances immune pathology and promotes chronic infection by limiting CD8(+) T-cell immunity

  作者 Lang, PA; Lang, KS; Xu, HFC; Grusdat, M; Parish, IA; Recher, M; Elford, AR; Dhanji, S; Shaabani, N; Tran, CW; Dissanayake, D; Rahbar, R; Ghazarian, M; Brustle, A; Fine, J; Chen, P; Weaver, CT; Klose, C; Diefenbach, A; Haussinger, D; Carlyle, JR; Kaech, SM; Maka, TW; Ohashi, PS  
  选自 期刊  Proceedings of the National Academy of Sciences of the United States of America;  卷期  2012年109-4;  页码  1210-1215  
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[摘要]Infections with HIV, hepatitis B virus, and hepatitis C virus can turn into chronic infections, which currently affect more than 500 million patients worldwide. It is generally thought that virus-mediated T-cell exhaustion limits T-cell function, thus promoting chronic disease. Here we demonstrate that natural killer (NK) cells have a negative impact on the development of T-cell immunity by using the murine lymphocytic choriomeningitis virus. NK cell-deficient (Nfil3(-/-), E4BP4(-/-)) mice exhibited a higher virus-specific T-cell response. In addition, NK cell depletion caused enhanced T-cell immunity in WT mice, which led to rapid virus control and prevented chronic infection in lymphocytic choriomeningitis virus clone 13- and reduced viral load in DOCILE-infected animals. Further experiments showed that NKG2D triggered regulatory NK cell functions, which were mediated by perforin, and limited T-cell responses. Therefore, we identified an important role of regulatory NK cells in limiting T-cell immunity during virus infection.

 
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