HLA-B27-restricted CD8 T cells derived from synovial fluids of patients with reactive arthritis and ankylosing spondylitis

Lancet. 1993 Sep 11;342(8872):646-50. doi: 10.1016/0140-6736(93)91760-j.


Ankylosing spondylitis and seronegative spondylarthropathies such as Reiter's syndrome and reactive arthritis are strongly associated with HLA-B27. However, the mechanisms by which HLA-B27 is involved in disease susceptibility and pathogenesis are unknown. If the disease association is a consequence of HLA-B27's physiological function in antigen presentation, the disease should be mediated by cytotoxic T lymphocytes (CTLs) that recognise bacterial or self peptides presented by HLA-B27. Proof of this arthritogenic peptide model requires isolation of B27-restricted CD8 T cells from arthritic joints of patients with spondylarthropathies. An important question is whether "arthritogenic" bacteria such as yersinia or salmonella can generate HLA-B27-restricted bacteria-specific CTLs. We describe such HLA-B27-restricted CTLs. We tested a panel of 354 alpha beta-TCR CD8 T lymphocyte clones (TLCs) that had been derived from the synovial fluid of 4 patients with reactive arthritis and 2 patients with ankylosing spondylitis. In 1 patient with yersinia-induced arthritis, 2 TLCs were identified that killed specifically yersinia-infected B27 target cells. In another patient with salmonella-induced arthritis, 1 B27-restricted CD8 TLC that recognised both salmonella and yersinia was identified. In 5 of the 6 patients autoreactive CTLs were found, 5 of which showed B27-restricted killing of uninfected cell lines. B27-restricted CTLs with specificity for arthritogenic bacteria or autoantigens provide a missing link in the pathogenesis of the HLA-B27-associated spondylarthropathies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Arthritis, Reactive / immunology*
  • Arthritis, Reactive / microbiology
  • CD8 Antigens / immunology
  • Chlamydia Infections
  • Clone Cells
  • HLA-B27 Antigen / immunology*
  • Humans
  • Male
  • Salmonella Infections
  • Salmonella typhimurium
  • Spondylitis, Ankylosing / immunology*
  • Spondylitis, Ankylosing / microbiology
  • Synovial Fluid / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Yersinia Infections
  • Yersinia enterocolitica


  • CD8 Antigens
  • HLA-B27 Antigen