Epitope specificity of clonally expanded populations of CD8+T cells found within the joints of patients with inflammatory arthritis

Objective. To investigate the hypothesis that clonality of synovial T cells from patients with rheumatoid arthritis is at least partly due to the pres ence of virus-specific T cells expressing a restricted repertoire of T cell receptors (TCRs). Methods. Using fluorescently labeled HLA class I-peptide tetramers, populat ions of virus-specific CD8+ T cells were identified in samples of periphera l blood and synovial fluid taken from 4 patients with inflammatory arthriti s. The TCR repertoire of the virus-specific T cells in the synovial fluid w as analyzed using a panel of TCR beta variable region-specific monoclonal a ntibodies. Where T cells expressing a particular V-beta chain dominated the response to a viral epitope, the sequences of these V-beta chains were der ived from sorted populations of antigen-specific T cells by reverse transcr ipt ion-polymerase chain reaction. Results. CD8+ T cells specific for Epstein-Barr virus, cytomegalovirus, and influenza virus were enriched in synovial fluid compared with peripheral b lood. Clonal or oligoclonal populations of CD8+ T cells were found to domin ate the responses to these viral epitopes in synovial fluid. Conclusion. The results support the hypothesis that restricted T cell recep tor usage by large populations of virus-specific T cells provides one expla nation for the presence of clonally expanded CD8+ T cells within the joints of patients with inflammatory arthritis. Thus, T cell clonality at a site of inflammation may reflect enrichment for memory T cells specific for fore ign antigens, rather than proliferation of autoreactive T cells specific fo r self antigens.