Identical T-cell expansions in the colon mucosa and the synovium of a patient with enterogenic spondyloarthropathy.
Intestinal T lymphocytes activated by antigen are suspected to play a key role in enterogenic spondyloarthropathies (SpA). Therefore, we aimed to identify and functionally characterize T-cell clones that are coexpanded in the intestinal mucosa and the synovium. Colon, peripheral blood, and synovium of a patient with enterogenic SpA were screened for clonal T-cell expansions by TCRB-CDR3 length analysis and sequencing. T-cell clones expanded in vivo were isolated from archived synovial cells by targeted T-cell cloning and characterized for phenotype, cytokine production, and antigen specificity. The synovial TCRBV18(+) T-cell repertoire of the patient was dominated by 2 CD8(+) T-cell clones using related CDR3. Both clones were expanded throughout the colon and were present in the peripheral blood. Upon in vitro stimulation with PDB/ionomycin, they showed predominantly interferon gamma and interleukin (IL)-4 but also tumor necrosis factor alpha and IL-10 production and did not specifically lyse autologous T-cell blasts, B-cell lines, or other autologous or allogeneic target or CD1d-transfected cells. These findings strongly suggest that T lymphocytes activated by antigen in the intestinal mucosa contribute to joint inflammation in enterogenic SpA by recognition of antigens specific for the inflamed synovium.
May
E
E
Internal Medicine II, University of the Saarland, Homburg/Saar, Germany.
Märker-Hermann
E
E
Wittig
B M
BM
Zeitz
M
M
Meyer zum Büschenfelde
K H
KH
Duchmann
R
R
D018528:ATP-Binding Cassette Transporters / Q000097:blood / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology; D002999:Clone Cells; D003106:Colon / Q000378:metabolism / Q000473:pathology*; D022801:Complementarity Determining Regions / Q000097:blood / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007410:Intestinal Diseases / Q000150:complications*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000097:blood / Q000235:genetics / Q000378:metabolism; D013122:Spinal Diseases / Q000209:etiology* / Q000473:pathology*; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000473:pathology*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology
D018528:ATP-Binding Cassette Transporters; D022801:Complementarity Determining Regions; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta