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

The inflamed synovium of rheumatoid arthritis (RA) patients contains γ/δ T cells which express predominantly T cell receptor (TcR) variable (Vδ1 and Vδ2 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 Vδ1‐Cδ and Vδ2‐Cδ chain cDNA, after using the polymerase chain reaction (PCR) to amplify TcR δ chain transcripts isolated from synovial membrane mononuclear cells (SMC) of five RA patients. The sequences of these δ 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, Vδ1 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 Vδ1 chain was less marked in SMC of two of these patients and absent in SMC of the other patients. For Vδ2, oligoclonality was detected in PBMC of two patients. In SMC of a single patient, a dominant Vδ2 transcript was detected that utilized the Jδ2 segment, which was rarely expressed in the normal TcR repertoire. These results indicate in vivo clonal expansion of Vδ1 and Vδ2‐expressing γ/δ T cells in the peripheral blood of RA patients and a synovial T cell infiltrate which consists largely of polyclonally expanded γ/δ T cells, but shows clonal dominance in some patients. Our data strongly support a role for Vδ1+ and Vδ2+ γ/β 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.