Common intra-articular T cell expansions in patients with reactive arthritis: Identical beta-chain junctional sequences and cytotoxicity toward HLA-B27

Spondyloarthropathies constitute a group of autoimmune diseases of special interest because of their tight association with the MHC class I molecule H LA-B27 and the bacterial triggering of some clinical forms called reactive arthritis (ReA), One current hypothesis is the presentation by HLA-B27 of a so-called arthritogenic peptide to T cells. To better focus on the relevan t T cell populations within the joint, we performed an extensive beta-chain T cell repertoire analysis of synovial fluid compared with PBL in seven pa tients, four of whom were characterized as having ReA triggered by Yersinia enterocolitica, Chlamydia trachomatis, or Shigella sonnei, Analysis of the size diversity of the beta-chain complementarity-determining region 3 (CDR 3) allowed us to evaluate the degree of T cell clonality in the samples. Ol igoclonal T cell expansions were frequently observed in the joint. In one p atient, CDR3 amino acid sequences of major expansions using two different B V genes were identical, One dominant T cell expansion and several CDR3 amin o acid sequences were identical in two different patients. Furthermore, one sequence was identical with a sequence reported independently in a Salmone lla-induced ReA patient. Together, these data indicate a surprisingly high degree of conservation in the T cell responses in recent-onset ReA triggere d by different micro-organisms. A CD8(+) synovial line expressing shared cl onotypes was established and reacted toward several B*2705 lymphoblastoid c ell lines, therefore supporting a molecular mimicry phenomenon at the T cel l level in the disease mechanism.