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  • Natural killer cell activat...
    Lang, Philipp A; Lang, Karl S; Xu, Haifeng C; Grusdat, Melanie; Parish, Ian A; Recher, Mike; Elford, Alisha R; Dhanji, Salim; Shaabani, Namir; Tran, Charles W; Dissanayake, Dilan; Rahbar, Ramtin; Ghazarian, Magar; Brüstle, Anne; Fine, Jason; Chen, Peter; Weaver, Casey T; Klose, Christoph; Diefenbach, Andreas; Häussinger, Dieter; Carlyle, James R; Kaech, Susan M; Mak, Tak W; Ohashi, Pamela S

    Proceedings of the National Academy of Sciences - PNAS, 01/2012, Volume: 109, Issue: 4
    Journal Article

    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.