V-ALPHA-GENE USAGE IN RHEUMATOID COMPARED WITH OSTEOARTHRITIC SYNOVIAL TISSUE T-CELLS

While many investigators have examined V gene usage by the clonotypic T-cell receptor (TCR) in rheumatoid arthritis (RA) joints, few have re ported on arthritic controls. We compared TCR alpha-chain V gene usage in knee synovial tissue specimens from 9 RA and 5 osteoarthritis (OA) patients. There was no significant difference in the number of V gene families used in RA compared with OA synovium. However, there was an increased prevalence of V alpha 28, V alpha 10, V alpha 17, and V alph a 18 and under representation of V alpha 15 in RA compared with OA syn ovium. Of these, V alpha 28 was also recently described by us as being present in RA synovial tissue early in the course of disease. V alpha 28 associated J region usage, and N-regional diversity was surveyed i n T-cell receptors from additional rheumatoid synovial tissue T-cell p opulations and normal peripheral blood. Oligoclonality was observed in 6/10 rheumatoid specimens either by direct sequencing or where three or more molecular clones were sequenced, compared with 0/5 normal PBMC s. The oligoclonal populations included 2/3 cell lines stimulated with interleukin-2 (IL-2) alone. Several novel J regions were observed, wi th some recurrent residues observed at N-region positions. These data indicate an increased prevalence of certain TCR V region families in R A versus OA synovium, and suggest an antigen-driven expansion of V alp ha 28-expressing T cells in RA synovium.