ANALYSIS OF REARRANGED T-CELL RECEPTOR (TCR) V-BETA TRANSCRIPTS IN LIVERS OF PRIMARY BILIARY-CIRRHOSIS - PREFERENTIAL V-BETA USAGE SUGGESTSANTIGEN-DRIVEN SELECTION

The presence of autoantibodies to mitochondrial pyruvate dehydrogenase complex-E2 (PDC-E2) and self-reactive T cells to PDC suggests that au toimmune mechanisms may be involved in the pathogenesis of primary bil iary cirrhosis (PBC). Molecular analysis of intrahepatic TCR repertoir e may provide valuable information on a T cell mechanism for PBC immun opathogenesis. We therefore analysed the TCR V beta usage in different regions of the livers removed during transplantation from two PBC pat ients. Using reverse transcription and polymerase chain reaction (RT-P CR), a limited heterogeneity of rearranged TCR V beta transcripts was demonstrated in different locations of the same liver. Sequence analys is of V beta-D beta-J beta (CDR3: the third complementarity determinin g region) showed the presence of conserved residues, no random N addit ions, and a common motif within CDR3. These results suggest that T cel ls homing to PBC liver may be antigen-driven. To elucidate further whe ther an immune deviation related to T helper 1 cell (Th1) or Th2 respo nses 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 a nd IFN-gamma could be amplified, whereas IL-4 was virtually undetectab le 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.