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RESEARCH ON THE IMMUNOPATHOLOGICAL MECHANISMS OF VOGT-KOYANAGI-HARADA DISEASE

VOGT-小柳-原田病的免疫病理机制研究

基本信息

批准号：
06671757
负责人：
NOROSE Kazumi
金额：
$ 1.15万
依托单位：
SHINSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671757/
关键词：
Vogt-koyanagi-harada disease Aqueous humor Flowcytimetry Uveitis Activatedt cells Fas Apoptosis Memory T cells

项目摘要

Vogt-Koyanagi-Harada disease (VKH) is thought to be a systemic disorder affecting various organs containing melanocytes. Melanocyte-specific cytotoxic T lymphocytes (CTL) in VKH have been assumed to be generated and to play an important role in the manifestation of this disease.We established melanoma-specific CTL cell lines from patients with VKH by long term culture of peripheral blood leukocytes with melanoma under IL-2 stimulation. The CTL activity of these cell lines against melanoma was inhibited by the anti-HLA-DR monoclonal antibody, whereas the monoclonal antibody specific for monomorphic determinants of HLA-A,B,and C failed to block lytic activity. Flow cytometric analysis revealed that the surface markers of these cell lines were CD4^+CD8^-HLA_-DR^+CD25^+TCRalphabeta^+TCRgammadelta^-. These cell lines produced extremely high level of IL-6 and Signifioant levels of IL-2 and IFN-gamma.mRNA of IL-2 was detected in the CTLs. Thus, melanoma-specific HLA-DR-restricted T-helper 1 CTLs may play a role in the immunopathogenesis of VKH.We assessed T cell subsets in the peripheral blood and aqueous humor from patients with VKH by using three-color flow cytometry. Although the percentage of CD4^+CD45RA^+ cells within T cells was rare in aqueous humor compared with peripheral blood, the percentage of CD4^+CD29^+ or CD4^+ CD45RO^+ (memory) cells in aqueous humor was much higher than in peripheral blood. Fas antigen, a cell-surface molecule that mediated apoptosis, was expressed preferentially on CD4^+CD45RO^+ cells in aqueous humor. Out results suggest that the accumulation of Fas^+CD4^+CD45RO^+ T lymphocytes in aqueous humor reflects the immunopathological mechanism of VKH.

沃格特-小柳-原田病 (VKH) 被认为是一种影响多种含有黑素细胞的器官的系统性疾病。据认为，VKH 中会产生黑色素细胞特异性细胞毒性 T 淋巴细胞 (CTL)，并在该疾病的表现中发挥重要作用。我们通过在 IL-2 刺激下长期培养黑色素瘤外周血白细胞，从 VKH 患者中建立了黑色素瘤特异性 CTL 细胞系。这些细胞系针对黑色素瘤的 CTL 活性受到抗 HLA-DR 单克隆抗体的抑制，而对 HLA-A、B 和 C 的单态决定簇特异的单克隆抗体则未能阻断裂解活性。流式细胞分析显示这些细胞系的表面标志物为CD4^+CD8^-HLA_-DR^+CD25^+TCRalphabeta^+TCRgammadelta^-。这些细胞系产生极高水平的IL-6以及显着水平的IL-2和IFN-γ。在CTL中检测到IL-2的mRNA。因此，黑色素瘤特异性 HLA-DR 限制性 T 辅助细胞 1 CTL 可能在 VKH 的免疫发病机制中发挥作用。我们使用三色流式细胞术评估了 VKH 患者外周血和房水中的 T 细胞亚群。尽管与外周血相比，房水中T细胞内CD4^+CD45RA^+细胞的百分比很少，但房水中CD4^+CD29^+或CD4^+CD45RO^+（记忆）细胞的百分比远高于外周血。 Fas抗原是一种介导细胞凋亡的细胞表面分子，优先在房水中的CD4^+CD45RO^+细胞上表达。结果表明，房水中Fas^+CD4^+CD45RO^+ T淋巴细胞的积累反映了VKH的免疫病理学机制。