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 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.


CONCLUSIONS
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.
Fazou
C
C
John Radcliffe Hospital, Oxford, UK.
Yang
H
H
McMichael
A J
AJ
Callan
M F
MF
D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D003586:Cytomegalovirus Infections / Q000276:immunology; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D020031:Epstein-Barr Virus Infections / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D015795:HLA-B8 Antigen / Q000276:immunology; D006801:Humans; D007251:Influenza, Human / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology*
D000956:Antigens, Viral; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D015795:HLA-B8 Antigen; D011948:Receptors, Antigen, T-Cell