Involvement of dendritic cells in pulmonary granuloma formation elicited by BCG in rats

树突状细胞参与卡介苗诱导的大鼠肺肉芽肿形成

• 批准号: 11670572
• 负责人: SUDA Takafumi
• 金额: $ 1.73万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670572/
• 关键词: dendritic cells; granuloma

Dendritic cells (DCs) are the most potent antigen-presenting cells and play a central role in initiating the primary immune response. However, their role in granulomatous inflammation has not been determined. The aim of this study was to elucidate the potential role of DCs in granuloma formation. Using a rat model of bacillus Calmette-Guerin (BCG)-elicited pulmonary granulomas, we investigated the distribution of DCs in the granulomas by immunohistochemistry with a rat-DC-specific monoclonal antibody, OX62. We found numerous large, pleiomorphic OX62^+ cells accumulating at the borders of the pulmonary granulomas, and these cells increased in number as the granulomas matured. The OX62^+ cells isolated from the granulomatous lung showed intense surface expression of MHC class II as well as the costimulatory molecules B7-1, B7-2 and a lack of T cell- and monocyte/macrophage-specific markers. Their ultrastructural morphology was characteristic of DCs. Functionally, they had potent capacity to stimulate allogeneic T cells and PPD-specific syngeneic T cells in the absence of exogenous peptides, and expressed high level of IL-12 p40 mRNA. Based on these findings, the OX62^+ cells infiltrating the granulomas were considered to be DCs expressing BCG-derived peptides. These results suggest that DCs participate in pulmonary granuloma formation elicited by BCG through their potent antigen-presenting function and cytokine production, providing a novel insight into DC function during T cell-mediated immune responses.

树突状细胞（Dendritic cells，DC）是最强的抗原提呈细胞，在启动初次免疫应答中起核心作用。然而，它们在肉芽肿性炎症中的作用尚未确定。本研究的目的是阐明DCs在肉芽肿形成中的潜在作用。使用大鼠模型卡介苗（BCG）引起的肺肉芽肿，我们研究了在肉芽肿的分布与大鼠DC特异性单克隆抗体，OX 62的免疫组化。我们发现在肺肉芽肿的边缘有大量的多形性OX 62 ^+细胞聚集，这些细胞的数量随着肉芽肿的成熟而增加。从肉芽肿性肺组织中分离的OX 62 ^+细胞表面表达大量的II类MHC和共刺激分子B7-1、B7-2，缺乏T细胞和单核细胞/巨噬细胞特异性标志物。其超微结构形态具有树突状细胞的特征。在功能上，它们具有在不存在外源肽的情况下刺激同种异体T细胞和PPD特异性同系T细胞的有效能力，并且表达高水平的IL-12 p40 mRNA。基于这些发现，浸润肉芽肿的OX 62 ^+细胞被认为是表达卡介苗衍生肽的DC。这些结果表明，DC通过其有效的抗原提呈功能和细胞因子的产生参与BCG引起的肺肉芽肿形成，为T细胞介导的免疫应答过程中DC功能提供了新的见解。

项目成果

Sato J, Suda T, et al.: "Migratory Patlers of thoracic duct lymphocytes into bronchus-associated lymphoid tissue of immunized rats"Lung. 178. 295-308 (2000)

Sato J、Suda T 等人：“胸导管淋巴细胞迁移到免疫大鼠的支气管相关淋巴组织中”肺。

Inui N, Chida K, Suda T, Nakamura H: "TH1/TH2 and TC1/TC2 profiles in peripheral blood and bronchoalveolar lavage fluid cells in pulmonary sarcoidosis"J Allergy Clin Immunol. 107(2). 337-44 (2001)

Inui N、Chida K、Suda T、Nakamura H：“肺结节病外周血和支气管肺泡灌洗液细胞中的 TH1/TH2 和 TC1/TC2 特征”J Allergy Clin Nutritionol。

Toyashima M.: "Wegener gramulomatosis responding to antituber culous drug"Chest. 119(2). 643-645 (2001)

Toyashima M.：“抗结核药物对韦格纳肉芽肿病的反应”胸部。

Ide K, Suda T, et al.: "Decreased expression of Th2 type cytokine mRNA contributes to the lack of allergic bronchial inflammation in aged rats"J Immunol. 163. 396-401 (1999)

Ide K、Suda T 等人：“Th2 型细胞因子 mRNA 的表达降低有助于老年大鼠过敏性支气管炎症的消失”J Nutrition。

Todate A, Chida K, Suda T, Imokawa S, Sato J, Ide K, Tsuchiya T, Inui N, Nakamura Y, Asada K, Hayakawa H, Nakamura H: "Increased numbers of dendritic cells in the bronchiolar tissues of diffuse panbronchiolitis"Am J Respir Crit Care Med. 162(1). 148-53 (2

Todate A、Chida K、Suda T、Imokawa S、Sato J、Ide K、Tsuchiya T、Inui N、Nakamura Y、Asada K、Hayakawa H、Nakamura H：“弥漫性全细支气管炎细支气管组织中树突状细胞数量增加”