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

利用白塞病患者眼液建立的T细胞克隆研究白塞病的致病机制

• 批准号: 08670543
• 负责人: SAGAWA Kimitaka
• 金额: $ 1.54万
• 依托单位: Kurume University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670543/
• 关键词: Behcet's disease; cloned T cells; T cell clones; cytokines; IL-8; TNF-alpha; hydrocortisone; FK506

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.

白塞氏病是一种全身性炎症性疾病，其免疫学特征为受影响组织（包括眼睛）中的CD 4 +T细胞和多形核细胞浸润。尽管广泛的研究，无论是病因还是发病机制的白塞氏病尚未澄清。为了更好地了解白塞病相关葡萄膜炎患者的免疫病理学，对2例白塞病相关葡萄膜炎患者的眼液（18个CD 3 + CD 4 + CD 8-克隆和4个CD 3 + CD 4-CD 8+克隆）和外周血单个核细胞（16个CD 3 + CD 4 + CD 8-克隆）中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659 pg/ml）或PBMC（536 pg/ml）中自发产生的IL-8水平显著高于健康供体PBMC（241 pg/ml）（分别为p<0.005和p<0.05）。至于其他细胞因子，IL-1 α、IL-2、IL-6、IL-10和TNF-α由来自白塞病患者的眼液的大多数TCC以低但可检测的量产生; IL-3、IFN-γ和GM-CSF也由一些TCC以低量产生;并且IL-4不由任何测试的TCC产生。TCC从眼液中产生的IL-8在PHA刺激后进一步上调，但被FK 506和氢化可的松抑制，但不被双氯芬酸钠抑制。秋水仙素可促进白塞病相关性葡萄膜炎患者外周血T细胞分泌IL-8，提示白塞病相关性葡萄膜炎患者外周血T细胞可能通过IL-8等细胞因子参与白塞病相关性葡萄膜炎的发病。

项目成果

Manabu Mochizuki, Levent Akduman, Robert B.Nussenblatt: "Behcet disease" In : Ocular Infection and Immunity. ed by Jay S.Pepose, Gary N.Holland, and Kirk R.Wlhelmus. Mosby, St. Louis. 663-675 (1997)

Manabu Mochizuki、Levent Akduman、Robert B.Nussenblatt：“白塞病”：眼部感染和免疫。

Kimitaka Sagawa: "Production of IL-8 and the other cytokines by T cell clones established from the ocular fluid of patients with Behcet's disease" Ocular Immunology and Inflammation. 3(2). 63-71 (1995)

Kimitaka Sakawa：“从白塞氏病患者的眼液中建立的 T 细胞克隆产生 IL-8 和其他细胞因子”《眼部免疫学和炎症》。

疋田 直文: "日本・英国におけるベーチェット病臨床像の検討" 日本眼科紀要. 47. 868-873 (1996)

Naofumi Hikita：“日本和英国白塞氏病的临床特征检查”日本眼科通报 47. 868-873 (1996)。

Kimitake Sagawa, Kyogo Itoh, Minako Sakaguchi, Makoto Tamai, Sunao Sugita, Naofumi Mukaida, Kouji Matsushima, Manabu Mochizuki: "Production of IL-8 and the other cytokines by T cell established from the ocular fluid of patients with Behcet's disease" Ocul

Kimitake Sakawa、Kyogo Itoh、Minako Sakaguchi、Makoto Tamai、Sunao Sugita、Naofumi Mukaida、Kouji Matsushima、Manabu Mochizuki：“从白塞氏病患者眼液中建立的 T 细胞产生 IL-8 和其他细胞因子”Ocul

Manabu-Mochizuki: "Immunotherapy for Behcet′s disease" Intern.Rev.Immunol.14. 49-66 (1997)

Manabu-Mochizuki：“白塞氏病的免疫疗法”Intern.Rev.Immunol.14 (1997)。