title: MHC class II-expressing hepatocytes function as antigen-presenting cells and activate specific CD4 T lymphocyutes.
abstract: The ability to activate CD4 T cells is restricted to antigen-presenting cells that express major histocompatibility complex (MHC) class II molecules. Parenchymal cells normally do not express MHC class II molecules; however, in clinical hepatitis, viral or autoimmune, hepatocytes often exhibit aberrant MHC class II expression. It is not known whether MHC class II-expressing hepatocytes can function as antigen-presenting cells, but it has been suggested that aberrant MHC class II expression by parenchymal cells may cause autoimmune disease. Therefore, we generated transgenic mice that specifically overexpress class II transactivator molecules in hepatocytes. Hepatocytes from these mice exhibited stable MHC class II expression and were used to stimulate CD4 T cells from T-cell receptor transgenic mice and CD4 T-cell lines. MHC II-expressing hepatocytes featured costimulatory CD80 molecules and could serve as antigen-presenting cells that were able to process protein antigen and to activate specific CD4 T cells. Nevertheless, the transgenic mice with aberrant hepatocellular MHC class II expression did not exhibit any symptoms of autoimmune disease. In conclusion, MHC II-expressing hepatocytes, as found in clinical hepatitis, can present antigen and activate CD4 T cells. The ability of hepatocytes to present antigen on MHC II molecules does not seem to be a sufficient cause for inflammatory autoimmunity and hepatitis. However, we still need to explore whether such antigen presentation is occurring in vivo. The transgenic mice described in this study may serve as a model to study the immune interaction of hepatocytes and CD4 T cells in both in vitro and in vivo.
authors.affiliation: I. Department of Medicine, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Herkel
authors.forename: Bettina
authors.initials: B
authors.lastname: Jagemann
authors.forename: Christiane
authors.initials: C
authors.lastname: Wiegard
authors.forename: Jose Francisco Garcia
authors.initials: JF
authors.lastname: Lazaro
authors.forename: Stefan
authors.initials: S
authors.lastname: Lueth
authors.forename: Stephan
authors.initials: S
authors.lastname: Kanzler
authors.forename: Manfred
authors.initials: M
authors.lastname: Blessing
authors.forename: Edgar
authors.initials: E
authors.lastname: Schmitt
authors.forename: Ansgar W
authors.initials: AW
authors.lastname: Lohse
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015870:Gene Expression / Q000276:immunology; D006505:Hepatitis / Q000276:immunology* / Q000503:physiopathology; D022781:Hepatocytes / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009687:Nuclear Proteins; D015534:Trans-Activators / Q000235:genetics
chemical_list: D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators