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.