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.