Impaired NK cell cytotoxicity by high level of interferon-gamma in concanavalin A-induced hepatitis.
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 51Cr 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-l cells in wild mice. Eight hours after NK 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 up-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.
Dong
Zhongjun
Z
Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Anhui, China.
Zhang
Cai
C
Wei
Haiming
H
Sun
Rui
R
Tian
Zhigang
Z
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002460:Cell Line; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology*; D003208:Concanavalin A / Q000633:toxicity*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004351:Drug Resistance; D005786:Gene Expression Regulation / Q000187:drug effects; D007371:Interferon-gamma / Q000097:blood* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016513:Mice, SCID; D055654:NK Cell Lectin-Like Receptor Subfamily C; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D011994:Recombinant Proteins
C527057:Klrc1 protein, mouse; C527086:Klrk1 protein, mouse; D055654:NK Cell Lectin-Like Receptor Subfamily C; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D011994:Recombinant Proteins; D003208:Concanavalin A; D007371:Interferon-gamma; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase