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

树突状细胞(DC)是最强大的抗原提呈细胞，在启动初始免疫反应中起着核心作用。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DC在肉芽肿形成中的潜在作用。采用卡介苗(BCG)诱导的大鼠肺肉芽肿模型，用大鼠DC特异性单抗OX62免疫组织化学方法研究了DC在肉芽肿内的分布。我们发现在肺肉芽肿边缘聚集了许多大的、多形性的OX62^+细胞，这些细胞的数量随着肉芽肿的成熟而增加。从肉芽肿性肺分离的OX62^+细胞表面强烈表达MHC-II类分子和共刺激分子B7-1、B7-2，缺乏T细胞和单核/巨噬细胞特异性标记。其超微结构形态具有DC的特征。在功能上，它们在没有外源性多肽的情况下具有较强的刺激同种异体T细胞和PPD特异性同种T细胞的能力，并表达高水平的IL-12p40mRNA。根据这些发现，浸润性肉芽肿的OX62^+细胞被认为是表达卡介苗多肽的DC。这些结果表明，DC通过其强大的抗原递呈功能和细胞因子的产生参与了卡介苗诱导的肺肉芽肿的形成，为研究DC在T细胞介导的免疫应答中的作用提供了新的视角。

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.