Journal
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
Volume 83, Issue 11, Pages 1045-1053Publisher
CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS
DOI: 10.1139/Y05-093
Keywords
cytotoxicity; hepatoimmunology; interferon-gamma; liver injury
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Unlike T cells, the role of natural killer (NK) cells is not well documented in the concanavalin (ConA)induced hepatitis model. This study aimed to investigate the regulatory effect of high levels of interferon-gamma (IFN-gamma) on NK cells in ConA-induced hepatitis. The cytotoxicities of NK cells from ConA-injected mice or NK cell lines (NK92 and NKL) were detected by the 4-h Cr-51 release assay. Depletion of NK cells with AsGM1 antibody was used to assess the NK cell role in ConA-induced hepatitis. Expression of NK cell receptors and cytotoxic molecules was measured by reverse transcription - polymerase chain reaction. Twelve hours after ConA injection, serum IFN-gamma was significantly increased in wild mice, but not in severe combined immunodeficiency mice, and hepatic NK cells exerted impaired cytotoxicity against YAC-1 cells in wild mice. Eight hours after INK cells were incubated in serum from ConA-treated mice, NK cell cytotoxicity was down-modulated and the effect was abolished by pretreatment with neutralizing serum IFN-gamma with specific antibody in vitro. A high concentration of IFN-gamma (> 1000 U/mL) inhibited the cytotoxicities of 2 NK cell lines in vitro, accompanied with down-regulation of NKG2D transcripts and Lip-regulation of NKG2A/B and KIR2DL transcripts. The inhibitive role of IFN-gamma was not seen in NKG2D ligand negative cells. These results suggest that NK cell cytotoxicity was inhibited by high levels of IFN-gamma in ConA-induced hepatitis, which may relate to the dispensable role of NK cells.
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