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

Abstract

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.