T cells in rheumatoid arthritis. Paradigms and facts.
Rheumatoid arthritis is characterized by a strong HLA-DRB1 association and a histologic picture consistent with an antigen recognition event by tissue-infiltrating T cells. Basic immunology has seen major progress in the understanding of the T-cell receptor-MHC-antigen interaction; however, the role of T cells and disease-associated HLA-DRB1 alleles in rheumatoid arthritis remains elusive. Recent studies on the genetics of the HLA-DRB1 association and the diversity of the repertoire of synovial T cells, and treatment studies with T-cell depleting antibodies, have suggested that the model of T cells recognizing an arthritogenic antigen in association with a HLA-DR molecule is too simplistic. The findings are more consistent with a regulatory role of T cells. Patients with rheumatoid arthritis have a unique T-cell repertoire that not only reflects the influence of disease-associated HLA-DRB1 alleles but also is greatly skewed by the clonal expansion of few CD4+ and CD8+ T-cell specificities. Understanding these repertoire changes appears to be promising not only in permitting understanding of the pathogenesis of this disease but also in designing T-cell-targeted treatment strategies.
Goronzy
J J
JJ
Mayo Clinic, Rochester, Minnesota, USA.
Weyand
C M
CM
D001172:Arthritis, Rheumatoid / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000502:physiology; D013583:Synovial Membrane / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D011948:Receptors, Antigen, T-Cell