HLA-B27-restricted CD8 T cells derived from synovial fluids of patients with reactive arthritis and ankylosing spondylitis.
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.
Hermann
E
E
First Department of Medicine, Johannes-Gutenberg-University of Mainz, Germany.
Yu
D T
DT
Meyer zum Büschenfelde
K H
KH
Fleischer
B
B
D000328:Adult; D016918:Arthritis, Reactive / Q000276:immunology* / Q000382:microbiology; D016827:CD8 Antigens / Q000276:immunology; D002690:Chlamydia Infections; D002999:Clone Cells; D015796:HLA-B27 Antigen / Q000276:immunology*; D006801:Humans; D008297:Male; D012480:Salmonella Infections; D012486:Salmonella typhimurium; D013167:Spondylitis, Ankylosing / Q000276:immunology* / Q000382:microbiology; D013582:Synovial Fluid / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D015009:Yersinia Infections; D015008:Yersinia enterocolitica
D016827:CD8 Antigens; D015796:HLA-B27 Antigen