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DOI: 10.1055/s-0033-1361041
NK cell activity promotes liver damage and chronic viral infection
Infections with hepatitis B virus and hepatitis C virus can turn into chronic infections, which currently affect more than millions of patients worldwide. Virus mediated T cell exhaustion results in limited T cell function thus promoting chronic virus infection and disease. Here we demonstrate that NK cells have a negative impact on the development of T cell immunity using the murine lymphocytic choriomeningitis virus (LCMV). NK cell deficient (nfil3-/-, E4BP4-/-) mice exhibited a higher virus specific T cell response. Accordingly, NK cell depletion caused enhanced viral induced hepatitis in WT mice when compared to NK cell deficient animals. This led to rapid virus elimination and prevented chronic viral infection in LCMV clone13 infected animals. Further experiments showed that NK cell derived perforin contributed to T cell dysfunction. In conclusion we identified an important role for regulatory NK cells (NKreg), in limiting T cell immunity during viral infection.