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

Arthritis Rheum. 2001 Sep;44(9):2038-45. doi: 10.1002/1529-0131(200109)44:9<2038::AID-ART353>3.0.CO;2-1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Viral / immunology
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / virology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Cytomegalovirus Infections / immunology
  • Epitopes
  • Epitopes, T-Lymphocyte / immunology*
  • Epstein-Barr Virus Infections / immunology
  • Female
  • Flow Cytometry
  • HLA-B8 Antigen / immunology
  • Humans
  • Influenza, Human / immunology
  • Male
  • Middle Aged
  • Receptors, Antigen, T-Cell / immunology
  • Synovial Membrane / cytology
  • Synovial Membrane / immunology*

Substances

  • Antigens, Viral
  • Epitopes
  • Epitopes, T-Lymphocyte
  • HLA-B8 Antigen
  • Receptors, Antigen, T-Cell