IMMUNOGENICITY OF RAT HEPATOCYTES IN-VIVO - EFFECT OF CHOLESTASIS-INDUCED CHANGES IN MAJOR HISTOCOMPATIBILITY COMPLEX EXPRESSION

Hepatocytes normally express few major histocompatibility complex (MHC ) class I and no MHC class II molecules, a phenomenon which could expl ain their low immunogenicity. However, in pathological situations, suc h as allograft rejection and cholestasis, hepatocytes strongly express MHC class I molecules and their immunogenicity could be different. Th e aim of this study was to assess the role of MHC expression on the im munogenicity of hepatocytes in vivo. Hepatocytes were obtained from no rmal and cholestatic DA rats by whole-liver perfusion with EDTA. Chole stasis was induced by ligation-section of the common bile duct. MHC ex pression on hepatocytes was assessed by cytofluorimetry after labellin g with monoclonal antibodies against MHC class I and class II antigens . The percentage of hepatocytes expressing MHC class I was 9.8 +/- 2.2 % in normal rats and 77.2 +/- 3.3% in cholestatic rats (P = 2 x 10(-4) ); MHC class II expression was present on 1 +/- 0. 5% of normal hepato cytes and 0.4% +/- 0.1% of cholestatic hepatocytes (P > 0.05). Lewis r ats received a DA or Wistar-Furth heart allograft 7 days after intrave nous,injection of 2 x 10(7) hepatocytes from normal or cholestatic DA rats. The DA heart allograft was rejected in 6.3 +/- 0.4 days in Lewis controls, 8.8 +/- 1.1 days (N.S.) in Lewis recipients that received n ormal DA hepatocytes and 17.6 +/- 3.0 days (P = 2 x 10(-4)) in Lewis r ecipients that received hepatocytes from cholestatic DA rats. The Wist ar-Furth heart allografts were rejected in 9.8 +/- 0.4 and 9.7 +/- 0.4 days (P > 0.05), respectively, in Lewis controls and those with chole static DA hepatocytes. These results confirm that hepatocytes are norm ally poorly immunogenic in vivo and suggest that they become tolerogen ic when MHC class I expression is induced. This could explain, at leas t partially, the relative tolerance of liver allografts.