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

PA Lang, KS Lang, HC Xu, M Grusdat… - Proceedings of the …, 2012 - National Acad Sciences
PA Lang, KS Lang, HC Xu, M Grusdat, IA Parish, M Recher, AR Elford, S Dhanji, N Shaabani
Proceedings of the National Academy of Sciences, 2012National Acad Sciences
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 …
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.
National Acad Sciences