Analysis of rearranged T cell receptor (TCR) Vβ transcripts in livers of primary biliary cirrhosis: Preferential Vβ 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 Vβ 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 Vβ transcripts was demonstrated in different locations of the same liver. Sequence analysis of Vβ-Dβ-Jβ (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-γ) was examined by the RT-PCR method. IL-2 and IFN-γ 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.