May E, Märker-Hermann E, Wittig B M, Zeitz M, Meyer zum Büschenfelde K H, Duchmann R
Internal Medicine II, University of the Saarland, Homburg/Saar, Germany.
Gastroenterology. 2000 Dec;119(6):1745-55. doi: 10.1053/gast.2000.20173.
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.
被抗原激活的肠道T淋巴细胞被怀疑在肠源性脊柱关节炎（SpA）中起关键作用。因此，我们旨在鉴定并在功能上表征在肠黏膜和滑膜中共扩增的T细胞克隆。通过TCRB - CDR3长度分析和测序，对一名肠源性SpA患者的结肠、外周血和滑膜进行克隆性T细胞扩增筛查。通过靶向T细胞克隆从存档的滑膜细胞中分离出体内扩增的T细胞克隆，并对其表型、细胞因子产生和抗原特异性进行表征。该患者的滑膜TCRBV18(+) T细胞库主要由2个使用相关CDR3的CD8(+) T细胞克隆主导。这两个克隆在整个结肠中均有扩增，并存在于外周血中。在用佛波酯/离子霉素进行体外刺激后，它们主要产生干扰素γ和白细胞介素（IL）-4，但也产生肿瘤坏死因子α和IL -10，并且不特异性裂解自体T细胞母细胞、B细胞系或其他自体或异体靶细胞或CD1d转染细胞。这些发现强烈表明，肠黏膜中被抗原激活的T淋巴细胞通过识别炎症滑膜特有的抗原，在肠源性SpA的关节炎症中起作用。
