Die Bedeutung natürlicher Killerzellen in der akuten Hepatitis C-Virusinfektion
Final Report Abstract
In summary, I have extensively studied the biology of Natural Killer cells and their role in hepatitis C virus infection. The results contribute to the understanding of the regulation of NK cell activation by KIR/HLA interaction and explain genetic associations between disease outcome and KIR/HLA genotypes and shed new light on the role of NK cells in the pathogenesis of HCV infection. In this context it is important to mention that the associations found between NK cell cytotoxicity and liver damage in chronic HCV infection were unexpected initially, as previous publications had only described altered phenotypes of NK cells in chronic HCV infection, but were unable to attribute their role in terms of progression of HCV infection. Surprisingly, the NK cell function was biased in favor of cytoxicity and against IFN-γ production. This is the first time it was described in humans and more importantly that this bias may actually contribute to the course of human disease. Consequently, we propose a model explaining how NK cells and their biased function in this infection contribute for the progression of chronic HCV infection.
Publications
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"Hepatic NK, NKT and T Cells". In: Gershwin ME, Vierling, JM and Manns MP - Liver Immunology - Principles and Practice. Humana Press, 2007; 71-82
Ahlenstiel G, Rehermann B
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"The liver as an immune organ". In: Adler G, Jia JD, Fan DM, LaRusso NF and Owyang C - Chronic Inflammation of Liver and Gut, Proceedings of the Falk Symposium 163. Springer 2008
Ahlenstiel G, Rehermann B
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Distinct KIR/HLA compound genotypes affect the kinetics of human antiviral natural killer cell responses. Journal of Clinical Investigation, 2008;118(3):1017-26
Ahlenstiel, Golo; Martin, Maureen P.; Gao, Xiaojiang; Carrington, Mary & Rehermann, Barbara
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Identification of CD4 T-cell epitopes in soluble liver antigen/liver pancreas autoantigen in autoimmune hepatitis. Gastroenterology, 2008; 135(6):2107-18
Mix, Heiko; Weiler–Normann, Christina; Thimme, Robert; Ahlenstiel, Golo; Shin, Eui–Cheol; Herkel, Johannes; David, Chella S.; Lohse, Ansgar W. & Rehermann, Barbara
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Natural killer cell function is intact after direct exposure to infectious hepatitis C virions. Hepatology, 2009; 49(1):12-21
Yoon, Joo Chun; Shiina, Masaaki; Ahlenstiel, Golo & Rehermann, Barbara
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Natural Killer Cells are Polarized towards Cytotoxicity in Chronic Hepatitis C in an Interferon-alpha-Dependent Manner. Gastroenterology, 2009 Sep 9. [Epub ahead of print]
Ahlenstiel, Golo; Titerence, Rachel H.; Koh, Christopher; Edlich, Birgit; Feld, Jordan J.; Rotman, Yaron; Ghany, Marc G.; Hoofnagle, Jay H.; Liang, T. Jake; Heller, Theo & Rehermann, Barbara
