Immunological and Molecular Biological Research on Local Defense System of the Eye

眼局部防御系统的免疫学和分子生物学研究

• 批准号: 10470368
• 负责人: MOCHIZUKI Manabu
• 金额: $ 7.94万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470368/
• 关键词: uveitis; apoptosis; soluble Fas ligand; soluble Fas; cytokines; aqueous humor; T cell clone; human; 局所防禦機構; HTLV-I; FPLCカラムクロマトグラフィー; 免疫抑制

The research was aimed at investigating the local defense system of the eye. The aqueous humor (AH) obtained from the anterior chamber of patients with age-related cataract during cataract surgery was found to suppress the cytokine production by T cell clones established from ocular infiltrating cells of patients with uveitis. Four molecules having the suppressive activities were identified from the AH by FPLC column chromatography. One of the four molecules had similar molecular weight as soluble Fas ligand (sFasL). A significant amount of sFasL was detected in the AH of age-related cataract patients, indicating the presence of sFasL in the AH of human eye at normal condition. In experimental model of uveitis, a significant correlation was found between the uveitis activity and the number of apoptotic cells or FasL-positive cells. These results suggest that sFasL and other immunosuppressive molecules in AH have a significant role to regulate intraocular inflammation. Further studies to examine if sFasL induces suppression of cytokine production or apoptosis of T cell clones established ocular infiltrating cells of uveitis patients are now ongoing at our laboratory.

该研究旨在研究眼睛的局部防御系统。在白内障手术期间从年龄相关性白内障患者的前房获得的房水（AH）被发现抑制由葡萄膜炎患者的眼浸润细胞建立的T细胞克隆的细胞因子产生。通过FPLC柱层析，从AH中鉴定出4个具有抑制活性的分子。其中一个分子的分子量与可溶性Fas配体（sFasL）相似。年龄相关性白内障患者的AH中检测到大量的sFasL，表明正常人的AH中存在sFasL。在实验性葡萄膜炎模型中，发现葡萄膜炎活动性与凋亡细胞或FasL阳性细胞的数量之间存在显著相关性。这些结果表明，sFasL和其他免疫抑制分子在AH中具有调节眼内炎症的重要作用。进一步的研究，以检查是否sFasL诱导抑制细胞因子的产生或T细胞克隆的细胞凋亡建立的葡萄膜炎患者的眼部浸润细胞，现在正在我们的实验室进行。

项目成果

Mami Sakaguchi, et al.: "Cytokine production by T cells infiltrating in the eye of uveitis patients."Japanese Journal of Ophthalmology. 42. 262-268 (1998)

Mami Sakaguchi 等人：“葡萄膜炎患者眼部浸润的 T 细胞产生细胞因子。”日本眼科杂志。

Ayako Ono, et al.: "Provirus load in patients with human T-cell leulemia virus type 1 uveitis correlates with precedent Graves'disease and disease activites"Japanese Journal of Cancer Research. 89. 608-614 (1998)

Ayako Ono 等人：“人类 T 细胞白血病病毒 1 型葡萄膜炎患者的原病毒载量与先前的格雷夫斯病和疾病活动相关”《日本癌症研究杂志》。

Naoko Seki, et al.: "Polymorphism of the 5'-flanking region of the tumor necrosis factor-α gene Susceptibility to human T-cell lymphotropic virus type I uveitis"Journal of Infectious Diseases. 180. 880-883 (1999)

Naoko Seki 等：“肿瘤坏死因子-α 基因 5-侧翼区域的多态性对人 T 细胞嗜淋巴细胞病毒 I 型葡萄膜炎的易感性”传染病杂志 180. 880-883 (1999)。

Mami Sakaguchi, et al.: "Cytokine production by T cells infiltrating in the eye of uveitis patients"Japanese Journal of Ophthalmology. 42. 262-268 (1998)

Mami Sakaguchi 等人：“葡萄膜炎患者眼睛中浸润的 T 细胞产生细胞因子”日本眼科杂志。

Jun Sueda, et al.: "Kinetics of apoptotic cells in experimental autoimmune uveoretinitis."Investigative Ophthalmology & Visual Science. (in press). 41 (2000)

Jun Sueda 等人：“实验性自身免疫性葡萄膜视网膜炎中凋亡细胞的动力学。”调查眼科