PERSISTENCE OF GAMMA DELTA T-CELL OLIGOCLONALITY IN THE PERIPHERAL-BLOOD OF RHEUMATOID-ARTHRITIS PATIENTS/

The peripheral blood of patients with rheumatoid arthritis (RA) contai ns oligoclonal gamma/delta T cell populations which may contribute to the pathogenesis of the disease. To investigate whether there is persi stent gamma/delta T cell oligoclonality in RA peripheral blood, we scr eened polymerase chain reaction-amplified T cell receptor (TCR) cDNA, derived from peripheral blood mononuclear cells (PBMC) of four RA pati ents, with sequence specific oligonucleotides (SSO). The SSO used were specific for TCR variable (V) delta 1, V delta 2 and V gamma 9 transc ripts comprising V-joining (J) junctions found over-represented in PBM C of the same RA patients, when bled up to 3 years previously. The dom inant transcripts were expressed in the new PBMC samples, although in most cases at a lower frequency than was originally detected. In one p atient there was almost 100% oligoclonality of V gamma 9-(N)-J gamma 2 junctional region sequences among the V gamma 9 cDNA clones, progress ing from 55% oligoclonality in 15 months. These results indicate the p ersistence of clonally expanded gamma/delta T cells in the peripheral blood of RA patients. Whether this reflects continual endogenous or ex ogenous antigenic stimulation remains to be investigated. The findings presented in this report may have important therapeutic implications in view of the potential for immune-intervention for the treatment of human autoimmune disorders, like RA.