A critical role for antigen-specific Th1 cells in acute liver injury in mice.
A novel liver injury model was established in mice by targeting of OVA-containing liposomes into the liver, followed by adoptive transfer of OVA-specific Th1 cells. Combined treatment of mice with OVA-containing liposomes and Th1 cell transfer caused an increase in serum transaminase activity that was paralleled with an elevation of serum IFN-gamma levels. In sharp contrast, OVA-specific Th2 cell transfer resulted in an increase of serum IL-4 levels, but did not induce liver injury. Neither NK, NK T, nor CD8+ T cells were required for the Th1-induced liver injury. The liver injury was blocked by anti-IFN-gamma mAb and anti-TNF-alpha mAb, but not by anti-Fas ligand mAb. The Fas/Fas ligand independency was also demonstrated using Fas-deficient lpr mice. These findings indicate that Th1 cells are the major effector cells in acute liver injury.
Nishimura
T
T
Section of Genetic Engineering, Research Center for Genetic Engineering and Cell Transplantation, Department of Immunology, Tokai University School of Medicine, Isehara, Japan. tak24@is.icc.u-tokai.ac.jp
Ohta
A
A
D000208:Acute Disease; D019264:Adoptive Transfer; D000818:Animals; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000502:physiology*; D053222:Fas Ligand Protein; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage / Q000276:immunology; D006520:Hepatitis, Animal / Q000209:etiology / Q000276:immunology / Q000473:pathology; D008024:Ligands; D008081:Liposomes / Q000008:administration & dosage / Q000276:immunology; D008099:Liver / Q000276:immunology* / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008819:Mice, Nude; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000637:transplantation; D019014:fas Receptor / Q000502:physiology
D018984:Epitopes, T-Lymphocyte; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006514:Hepatitis B Surface Antigens; D008024:Ligands; D008081:Liposomes; D008562:Membrane Glycoproteins; D019014:fas Receptor; D010047:Ovalbumin