Study on the pathogenic mechanism of Behcet's disease using T cell clones established from the ocular fluid of the patients with Behcet's disease

白塞病是一种全身性炎症性疾病，免疫学特征是CD4T细胞和多形核细胞在包括眼睛在内的受影响组织中的渗透。尽管进行了广泛的研究，但白塞病的病因和发病机制尚不清楚。为更好地了解白塞病葡萄膜炎的免疫病理机制，对2例白塞病葡萄膜炎患者的眼液(18个CD3、CD4、CD8、4个CD3、CD8、CD8)和外周血单个核细胞(PBMC)(16个CD3、CD4、CD8)T细胞克隆(TCC)产生细胞因子进行了研究。TCC从患者眼液(平均659pg/ml)或外周血单核细胞(536pg/ml)自发产生IL-8的水平(P<0.005)显著高于TCC从健康献血员PBMC产生的IL-8水平(241pg/ml)。对于其他细胞因子，白塞病患者眼液中大多数移行细胞癌产生IL-1α、IL-2、IL-6、IL-10和TNF-α，部分移行细胞癌也有少量产生IL-3、干扰素-γ和GM-CSF，所有受检移行细胞癌均不产生IL-4。PHA刺激TCC产生IL-8进一步上调，但FK506和氢化可的松抑制IL-8的产生，但不受双氯芬酸钠的抑制。秋水仙碱反而增加了白塞病相关葡萄膜炎的IL-8的产生。这些结果表明，白塞病相关葡萄膜炎的发病机制中，受累组织和PBMC中的T细胞可能通过IL-8和其他细胞因子发挥重要作用。

Behcet's disease is a systemic inflammatory disease immunologically characterized by the infiltration of CD4+T cells and polymorphonuclear cells in the affected tissues, including the eye. Despite extensive studies, neither the etiology nor the pathogenic mechanism of Behcet's disease has been clarified. Production of cytokines by T cell clones (TCC) from the ocular fluid (18 CD3+CD4+CD8- clones and 4 CD3+CD4-CD8+clones) and peripheral blood mononuclear cells (PBMC) (16 CD3+CD4+CD8- clones) of two patients with uveitis associated with Behcet's disease was investigated to understand better the immunopathology of the disease. The level of IL-8 spontaneously produced by TCC from the ocular fluid (mean : 659 pg/ml) or PBMC (536 pg/ml) of the patients was significantly higher (p<0.005, and p<0.05, respectively) than that by TCC from PBMC of healthy donors (241 pg/ml). As for the other cytokines, IL-1alpha, IL-2, IL-6, IL-10, and TNF-alpha were produced at low but detectable amounts by the majority of TCC from the ocular fluid of patients with Behcet's disease ; IL-3, IFN-gamma and GM-CSF were also produced by some of TCC at low amounts ; and IL-4 was not produced by any TCC tested. IL-8 production by TCC from the ocular fluid was further up-regulated upon stimulation with PHA,but was suppressed by FK506 and hydrocortisone, though not by diclofenac sodium. Colchicine rather increased IL-8 production by these TCC.These results suggest that T cells in both the affected tissues and PBMC play an important role in the pathogenesis of uveitis associated with Behcet's disease through IL-8 and probably the other cytokines.