Analysis of rearranged T cell receptor (TCR) V beta transcripts in livers of primary biliary cirrhosis: preferential V beta usage suggests antigen-driven selection.
The presence of autoantibodies to mitochondrial pyruvate dehydrogenase complex-E2 (PDC-E2) and self-reactive T cells to PDC suggests that autoimmune mechanisms may be involved in the pathogenesis of primary biliary cirrhosis (PBC). Molecular analysis of intrahepatic TCR repertoire may provide valuable information on a T cell mechanism for PBC immunopathogenesis. We therefore analysed the TCR V beta usage in different regions of the livers removed during transplantation from two PBC patients. Using reverse transcription and polymerase chain reaction (RT-PCR), a limited heterogeneity of rearranged TCR V beta transcripts was demonstrated in different locations of the same liver. Sequence analysis of V beta-D beta-J beta (CDR3: the third complementarity determining region) showed the presence of conserved residues, no random N additions, and a common motif within CDR3. These results suggest that T cells homing to PBC liver may be antigen-driven. To elucidate further whether an immune deviation related to T helper 1 cell (Th1) or Th2 responses may exist in PBC, intrahepatic mRNA expression of IL-2, IL-4 and interferon-gamma (IFN-gamma) was examined by the RT-PCR method. IL-2 and IFN-gamma could be amplified, whereas IL-4 was virtually undetectable in the livers from the two patients with PBC. The findings suggest that polarization of intrahepatic lymphokine expression toward the Th1-dominant pattern may be significant in the immunopathogenesis of PBC.
Tsai
S L
SL
Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung Medical College, Taipei, Taiwan.
Lai
M Y
MY
Chen
D S
DS
D000595:Amino Acid Sequence; D001483:Base Sequence; D017124:Conserved Sequence; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000276:immunology*; D006801:Humans; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007371:Interferon-gamma / Q000032:analysis; D007376:Interleukin-2 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D008105:Liver Cirrhosis, Biliary / Q000235:genetics* / Q000276:immunology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D005810:Multigene Family; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000276:immunology*
D007133:Immunoglobulin Joining Region; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma