Persistence of γ/δ T cell oligoclonality in the peripheral blood of rheumatoid arthritis patients

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Abstract
Summary: The peripheral blood of patients with rheumatoid arthritis (RA) contains oligocional γ/δ T cell populations which may contribute to the pathogenesis of the disease. To investigate whether there is persistent γ/δ T cell oligoclonality in RA peripheral blood, we screened polymerase chain reaction‐amplified T cell receptor (TCR) cDNA, derived from peripheral blood mononuclear cells (PBMC) of four RA patients, with sequence specific oligonucleotides (SSO). The SSO used were specific for TCR variable (V)δ1, Vδ2 and Vγ9 transcripts comprising V‐joining (J) junctions found over‐represented in PBMC of the same RA patients, when bled up to 3 years previously. The dominant transcripts were expressed in the new PBMC samples, although in most cases at a lower frequency than was originally detected. In one patient there was almost 100% oligoclonality of Vγ9‐(N)‐Jγ2 junctional region sequences among the Vγ9 cDNA clones. progressing from 55% oligoclonality in 15 months. These results indicate the persistence of clonally expanded γ/δ T cells in the peripheral blood of RA patients. Whether this reflects continual endogenous or exogenous antigenic stimulation remains to be investigated. The findings presented in this report may have important therapeutic implications in view of the potential for immuno‐intervention for the treatment of human autoimmune disorders, like RA.