Evidence for oligoclonality of T cell receptor delta chain transcripts expressed in rheumatoid arthritis patients

Abstract

The inflamed synovium of rheumatoid arthritis (RA) patients contains gamma/delta T cells which express predominantly T cell receptor (TcR) variable (V) delta 1 and V delta 2 chains. Such T cells may contribute to the pathogenesis of RA. To assess the extent of clonality among these T cell populations we sequenced the junctional regions of rearranged TcR V delta 1-C delta and V delta 2-C delta chain cDNA, after using the polymerase chain reaction (PCR) to amplify TcR delta chain transcripts isolated from synovial membrane mononuclear cells (SMC) of five RA patients. The sequences of these delta chain transcripts were compared with those found in peripheral blood mononuclear cells (PBMC) of the same patients and in PBMC of four healthy controls. In contrast to control PBMC, V delta 1 chain cDNA derived from PBMC of three patients showed a strong bias towards usage of the same V-joining (J) combination and junctional region sequences, although the specific sequences were unique in each patient. However, oligoclonality of the V delta 1 chain was less marked in SMC of two of these patients and absent in SMC of the other patients. For V delta 2, oligoclonality was detected in PBMC of two patients. In SMC of a single patient, a dominant V delta 2 transcript was detected that utilized the J delta 2 segment, which was rarely expressed in the normal TcR repertoire. These results indicate in vivo clonal expansion of V delta 1- and V delta 2-expressing gamma/delta T cells in the peripheral blood of RA patients and a synovial T cell infiltrate which consists largely of polyclonally expanded gamma/delta T cells, but shows clonal dominance in some patients. Our data strongly support a role for V delta 1+ and V delta 2+ gamma/delta T cells in the pathogenesis of RA, and, although the nature of the antigen(s) recognized by these cells remains elusive, this report suggests the potential involvement of antigen(s) specific for the V region and V-J junction.