title: Requirement of IL-4 and liver NK1+ T cells for concanavalin A-induced hepatic injury in mice.
abstract: Con A-induced hepatic injury of mice accompanied by elevated transaminase was inhibited after in vivo depletion of liver NK cells and NK1+ T cells with intermediate TCR by anti-NK1 Ab or anti-IL-2Rbeta Ab. However, depletion of liver NK cells alone by anti-asialo-GM1 Ab did not inhibit hepatic injury. Although depletion of NK1+ T cells inhibited Con A-induced IL-2R expression of CD4+ high TCR (TCRhigh) cells and IL-4 mRNA expression of hepatic mononuclear cells, exogenous IL-4 engendered Con A-induced hepatic injury and endowed the expression of IL-2R of CD4+ TCRhigh cells. It was also found that in vivo treatment with anti-IL-4 Ab before Con A administration inhibited Con A-induced hepatic injury. In addition, although Con A did not induce hepatic injury in MHC class I-deficient mice, exogenous IL-4 again engendered severe hepatic injury in these mice. Further, while serum TNF-alpha levels induced by Con A were greatly decreased in NK1+ T cell-depleted mice and class I-deficient mice, TNF-alpha levels were recovered by exogenous IL-4. These findings reveal that although CD4+ TCRhigh cells in the liver and their production of TNF-alpha are the direct effectors of Con A-induced hepatic injury, liver NK1+ T cells also play an important role in this hepatitis model. Con A hepatitis may serve as an experimental model for human autoimmune hepatitis.
authors.affiliation: Department of Immunology, Niigata University School of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Toyabe
authors.forename: S
authors.initials: S
authors.lastname: Seki
authors.forename: T
authors.initials: T
authors.lastname: Iiai
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.forename: K
authors.initials: K
authors.lastname: Shirai
authors.forename: H
authors.initials: H
authors.lastname: Watanabe
authors.forename: H
authors.initials: H
authors.lastname: Hiraide
authors.forename: M
authors.initials: M
authors.lastname: Uchiyama
authors.forename: T
authors.initials: T
authors.lastname: Abo
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D000941:Antigens / Q000502:physiology*; D000954:Antigens, Surface; D003208:Concanavalin A / Q000633:toxicity*; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D015847:Interleukin-4 / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D037181:Lectins, C-Type; D008099:Liver / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D000954:Antigens, Surface; D015395:Histocompatibility Antigens Class I; C527203:KLRB1 protein, human; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D015847:Interleukin-4