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

ABSTRACT

OBJECTIVE: To investigate the hypothesis that clonality of synovial T cells from patients with rheumatoid arthritis is at least partly due to the presence of virus-specific T cells expressing a restricted repertoire of T cell receptors (TCRs). METHODS: Using fluorescently labeled HLA class I-peptide tetramers, populations of virus-specific CD8+ T cells were identified in samples of peripheral blood and synovial fluid taken from 4 patients with inflammatory arthritis. The TCR repertoire of the virus-specific T cells in the synovial fluid was analyzed using a panel of TCR beta variable region-specific monoclonal antibodies. Where T cells expressing a particular Vbeta chain dominated the response to a viral epitope, the sequences of these Vbeta chains were derived from sorted populations of antigen-specific T cells by reverse transcription-polymerase chain reaction. RESULTS: CD8+ T cells specific for Epstein-Barr virus, cytomegalovirus, and influenza virus were enriched in synovial fluid compared with peripheral blood. Clonal or oligoclonal populations of CD8+ T cells were found to dominate the responses to these viral epitopes in synovial fluid. CONCLUSION: The results support the hypothesis that restricted T cell receptor usage by large populations of virus-specific T cells provides one explanation 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 foreign antigens, rather than proliferation of autoreactive T cells specific for self antigens.