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 explain their low immunogenicity. However, in pathological situations, such as allograft rejection and cholestasis, hepatocytes strongly express MHC class I molecules and their immunogenicity could be different. The aim of this study was to assess the role of MHC expression on the immunogenicity of hepatocytes in vivo. Hepatocytes were obtained from normal and cholestatic DA rats by whole-liver perfusion with EDTA. Cholestasis was induced by ligation-section of the common bile duct. MHC expression on hepatocytes was assessed by cytofluorimetry after labelling 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 hepatocytes and 0.4% +/- 0.1% of cholestatic hepatocytes (P > 0.05). Lewis rats received a DA or Wistar-Furth heart allograft 7 days after intravenous 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 normal DA hepatocytes and 17.6 +/- 3.0 days (P = 2 x 10(-4)) in Lewis recipients that received hepatocytes from cholestatic DA rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Arvieux
C
C
INSERM U 181, Hôpital Saint-Antoine, Paris.
Calmus
Y
Y
Gane
P
P
Legendre
C
C
Mariani
P
P
Delelo
R
R
Poupon
R
R
Nordlinger
B
B
D000818:Animals; D000917:Antibody Formation; D002779:Cholestasis / Q000276:immunology* / Q000503:physiopathology*; D015870:Gene Expression / Q000235:genetics; D006084:Graft Rejection / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000235:genetics; D007275:Injections, Intravenous; D008099:Liver / Q000166:cytology* / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000235:genetics* / Q000276:immunology; D008297:Male; D009206:Myocardium / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D014184:Transplantation, Homologous
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II