Cell-mediated cytotoxicity of sensitized spleen cells against target liver cells--in vivo and in vitro study with a mouse model of experimental autoimmune hepatitis.
Spleen cells obtained from C57BL/6 (B6) mice with an experimental autoimmune hepatitis were transferred to normal C57BL/6 recipient mice. Most prominent liver damages occurred in the recipient mice injected with sensitized nylon wool column-adherent spleen cells from the donor mice. Production of such liver damage was blocked by treatment of the sensitized adherent spleen cells with anti-Thy 1,2 monoclonal antibody and complement before injection. Based on these in vivo results, a microcytotoxicity assay was performed using isolated C57BL/6 hepatocytes as target cells and sensitized spleen cells obtained from hepatitis donor mice as effector cells. The fraction of sensitized nylon wool-adherent spleen cells demonstrated a high cytotoxic activity against isolated syngeneic hepatocytes, although the other fractions and spleen cells of control animals showed no such effect. The cytotoxic activity of sensitized-adherent spleen cells against target hepatocytes was significantly reduced after treatment with anti-Thy 1,2 antibody and complement, but it increased after depletion of B cells and Fc receptor-bearing T-cells. Although these sensitized nylon wool-adherent spleen cells showed high cytotoxic activities against syngeneic hepatocytes, their cytotoxicity against allogeneic hepatocytes was lower. They exerted no cytotoxic activity against syngeneic renal glomerular cells and EL-4 thymoma cells. These results suggest that sensitized T-cells in the nylon wool column-adherent fraction play the role of cytotoxic killer cells against target liver cells in vitro.
D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006505:Hepatitis / Q000276:immunology*; D007111:Immunity, Cellular; D008099:Liver / Q000166:cytology / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology*
D001323:Autoantibodies; D008565:Membrane Proteins; D011506:Proteins