T cell receptor gene rearrangements of T lymphocytes infiltrating the liver in chronic active hepatitis B and primary biliary cirrhosis (PBC): oligoclonality of PBC-derived T cell clones.
Immunological events are involved in the pathophysiology of chronic active hepatitis as indicated from the accumulation of T lymphocytes at the site of tissue damage. We generated T cell clones from liver biopsies of 3 patients with chronic active hepatitis B and 2 patients with primary biliary cirrhosis. These T cell clones (n = 84) were analyzed by means of T cell receptor (TcR) beta gene rearrangements to determine whether the infiltrate consists of a polyclonal or oligoclonal T cell population. The vast majority (62 of 64) of T cell clones from three different patients with chronic active hepatitis B showed no identical rearrangements of the TcR beta chain genes. In marked contrast, in both patients with primary biliary cirrhosis, T cell clones established were of limited diversity. Thus 5 out of 10 and 2 out of 10 T cell clones from one patient and 3 out of 9 and 2 out of 9 T cell clones from the second patient, respectively, showed identical TcR beta gene rearrangements. These data suggest that a clonal dominance is characteristic for local T cell responses in autoimmune liver disease such as primary biliary cirrhosis whereas in virus-induced chronic active hepatitis T cell activation occurs polyclonally.
Moebius
U
U
Abteilung Angewandte Immunologie, Deutsches Krebsforschungszentrum, Heidelberg, FRG.
Manns
M
M
Hess
G
G
Kober
G
G
Meyer zum Büschenfelde
K H
KH
Meuer
S C
SC
D000328:Adult; D000368:Aged; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001327:Autoimmune Diseases / Q000209:etiology; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens; D002999:Clone Cells; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D006521:Hepatitis, Chronic / Q000276:immunology*; D006801:Humans; D008099:Liver / Q000473:pathology*; D008105:Liver Cirrhosis, Biliary / Q000276:immunology*; D008875:Middle Aged; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens