RESERCH ON THE RELATIONSHIP BETWEEN THE CELLULAR IMMUNITY AND CLINCAL PICTURE ON VOGT-KOYANAGI-HARADA DISEASE.

VOGT-小柳-原田病细胞免疫与临床表现之间关系的研究。

• 批准号: 04671070
• 负责人: NOROSE Kazumi
• 金额: $ 1.28万
• 依托单位: DEPARTMENT OF OPHTHALMOLOGY, 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: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04671070/
• 关键词: Vogt-Koyanagi-Harada disease; Cellular immunity; Cytotoxic T cell; IL-6; Uveitis; Aqueous humor; Hybridoma

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.In this study, we analyzed the blocking effects of anti-HLA class I and anti-HLA calss II antibodies against the cytotoxicity of human melanoma cell line(P-36)-specific CTL.Cytoxicities against P-36 were assayd by % specific ^<51>Cr release. The cytotoxicity against P-36 was blocked by anti-HLA calss II antibody but not by anti-HLA class I antibody. From these results P-36-specific CTL recognized the complex of melanoma antigen and HLA-class II molecules of P-36. Furthermore, we established a melanoma-specific CTL cell line(SF-1) from a patient with VKH by long term culture of peripheral blood leukocytes with P-36 under IL-2 stimulation. SF-1 showed strong cytotoxicity against P-36. Flow cytometric analysis revealed that the surface markers of SF-1 were CD4^+CD8^-HLA-DR^+CD25^+TCRalphabeta^+TCRgammadelta^-. SF-1 produced extreamly high level of IL-6 and significant levels of IL-2 and IFN-gamma. Thus, lymphokines produced by melanoma-specific CTL may play an important role in the immunopathogenesis of VKH.Additionaly, we established hybridomas of SF-1 and T cell tumor cell line(CEM). The surface markers of the hybridomas were CD2^+CD4^+CD8^-CD25^<(〕SY.+-.〔)>HLA-DR^-TCRalphabeta^<(〕SY.+-.〔)>TCRgammadelta^-CD11a^+CD28^+. Although these hybridomas adhered to P-36, it did not show cytotoxicity against P-36 and IL-2, IL-6 and IFN-gamma were not detected in the supernate of these hybridomas.

Vogt-Koyanagi-Harada病（VKH）被认为是一种影响含有黑素细胞的各种器官的全身性疾病。VKH中产生的黑素细胞特异性细胞毒性T淋巴细胞（CTL）在VKH的发病中起重要作用，本文分析了抗HLA-I类和抗HLA-II类抗体对人黑色素瘤细胞系（P-36）特异性CTL细胞毒性的阻断作用，并以%特异性γ-Cr释放法测定了对P-36的细胞毒性<51>。抗HLA Ⅱ类抗体可阻断P-36的细胞毒作用，而抗HLA Ⅰ类抗体则不能阻断P-36的细胞毒作用。根据这些结果，P-36特异性CTL识别黑素瘤抗原和P-36的HLA-II类分子的复合物。此外，我们建立了一个黑色素瘤特异性CTL细胞系（SF-1）从VKH患者的外周血白细胞与P-36在IL-2刺激下长期培养。SF-1对P-36有较强的细胞毒作用。流式细胞术分析显示SF-1的表面标志物为CD 4 ^+ CD 8 ^-HLA-DR^+ CD 25 ^+ TCR α ^+ TCR γ δ ^-。SF-1产生极高水平的IL-6和显著水平的IL-2和IFN-γ。因此，黑色素瘤特异性CTL产生的淋巴因子可能在VKH的免疫发病机制中起重要作用。杂交瘤的表面标志物为CD 2 + CD 4 + CD 8 + CD 25+。（）&gt;HLA-DR-TCR α &lt;（）SY. ±-。（）&gt; TCR γ δ ^-CD11a^+CD28^+。尽管这些杂交瘤粘附于P-36，但其不显示针对P-36的细胞毒性，并且在这些杂交瘤的上清液中未检测到IL-2、IL-6和IFN-γ。

项目成果

Yano A,et al: "Antigen presentation by Toxoplasma-infected cells:Antigen entry through cell membrane fusion." Int Arch Allergy Immunol. 98. 13-17 (1992)

Yano A 等人：“弓形虫感染细胞的抗原呈递：抗原通过细胞膜融合进入。”

Nrose K: "Vogt-Koyanagi-Harada disease." Shinshu Med J. 41. 555-564 (1993)

Nrose K：“沃格特-小柳-原田病。”

Norose K,et al: "Dominance of activated T cells and interleukin-6 in aqueous humor in Vogt-Koyanagi-Harada disease." Invest Ophthalmol Vis Sci. 35. 33-39 (1994)

Norose K 等人：“Vogt-Koyanagi-Harada 病中房水中活化 T 细胞和白细胞介素 6 的优势。”

Aosai F,et al: "Isolation of naturally processed peptides from Toxoplasma-gondii-infected human B lymphoma as recognized by cytotoxic T lymphocytes." J Parasitol. (in press).

Aosai F 等人：“从弓形虫感染的人 B 淋巴瘤中分离出自然加工的肽，并被细胞毒性 T 淋巴细胞识别。”

野呂瀬一美: "Vogt-小柳-原田病" 信州医誌. 41. 555-564 (1993)

Kazumi Norose：“Vogt-小柳-原田病”《信州医学杂志》41. 555-564 (1993)。