Z Gastroenterol 2014; 52 - P_5_32
DOI: 10.1055/s-0033-1361041

NK cell activity promotes liver damage and chronic viral infection

PA Lang 1, HC Xu 1, M Grusdat 1, I Parish 4, M Recher 5, A Elford 2, S Dhanji 2, N Shaabani 3, CW Tran 2, D Dissanayake 2, R Rahbar 2, M Ghazarian 2, A Brustle 2, J Fine 8, P Chen 8, CT Weaver 6, C Klose 7, A Diefenbach 7, JR Carlyle 8, SM Kaech 4, TW Mak 2, PS Ohashi 2, D Häussinger 1, KS Lang 3
  • 1Heinrich Heine University, Department of Gastroenterology, Hepatology, and Infectious Diseases, Düsseldorf, Germany
  • 2University of Toronto, Ontario Cancer Institute, Toronto, Canada
  • 3University of Essen, Institute of Immunology, Essen, Germany
  • 4Yale Medical School, Department of Immunobiology, New Haven, USA
  • 5University Hospital Basel, Clinic for Primary Immunodeficiency, Basel, Switzerland
  • 6University of Alabama at Birmingham, Department of Pathology, Birmingham, USA
  • 7University of Freiburg, Institute of Medical Microbiology and Hygiene, Freiburg, Germany
  • 8University of Toronto, Department of Immunology, Toronto, Canada

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.