PULMONARY SARCOIDOSIS AND BERYLLIOSIS IMMUNOPATHOGENESIS

结节病和慢性铍病是慢性肉芽肿性纤维化。 具有显著临床和组织病理学特征的疾病 作为局部(肺)和全身免疫异常。这样做的目的是 研究是对这些疾病进行平行研究，以便 阐明免疫致病事件。有四个相互关联的领域 调查的结果。首先，确定表型特征和 免疫效应细胞的功能可从损伤部位恢复 炎症累及(肺)和血液。这些研究将进行 以一种连续的预测方式来确定是否有一种关系 在这些研究和疾病解决的进展之间。第二，我们 将检验T淋巴细胞抗体的假设，T淋巴细胞已经被 如前所述，改变免疫的数量、身份或功能 调节性T细胞，并导致观察到的免疫异常 结节病。第三个相关领域是对附属细胞的研究 肺(肺泡巨噬细胞)和血液巨噬细胞的功能 病人。这将检验巨噬细胞在影响 免疫调节性T细胞的活化程度和功能 阿龙。具体来说，巨噬细胞的功能，如释放 白细胞介素1和对淋巴细胞增殖的影响，将被检测。 该提案的最终目标将是开发出体外系统，用于 抗原反应性T细胞克隆的刺激和长期培养 两种疾病都有。这将利用这样一个事实，即有一个 活化T细胞在肺内的蓄积及其初步研究 提示利用T细胞生长因子建立 连续的T细胞系在这两种疾病中都是可行的。我们将尝试 建立抗原特异性T细胞克隆的体外检测方法 抗原(铍盐和Kveim抗原的标准化制备) 和自体辅助饲养层细胞。这样做的长期目标是 这项研究的组成部分将是开发一种Kveim的体外检测方法 抗原，并开始识别可能包含的假定抗原 在克维姆的准备工作中。这些调查是一项长期调查的一部分 对间质性和纤维性肺疾病感兴趣，是 医院的间质性肺病计划(和结节病诊所)。 是一所大学。爸爸的名字。

Sarcoidosis and chronic berylliosis are chronic granulomatous fibrotic diseases that share striking clinical and histopathologic features as well as local (lung) and systemic immune abnormalities. The objective of this study is to conduct parallel studies of these diseases in order to elucidate the immunopathogenetic events. There are four interrelated areas of investigation. First, to characterize the phenotypic identity and function of immune effector cells that can be recovered from sites of inflammatory involvement (lung) and blood. These studies will be conducted in a serial prospecitve fashion to determine if there is a relationship between these studies and progression of resolution of disease. Second, we will test the hypothesis that antibodies to T lymphocytes, which have been previously described, alter the number, identity or function of immune regulatory T cells and contribute to the immune abnormalities observed in sarcoidosis. A third related area is the study of the accessory cell function for lung (alveolar macrophages) and blood macrophages in these patients. This will examine the role of macrophages in influencing the degree of activation and function of immunoregulatory T cells found in the lung. Specifically, macrophage functions, such as the release of Interleukin-1 and effect on lymphocyte proliferation, will be examined. The final aim of the proposal will be to develop in vitro systems for the stimulation and long-term cultivation of antigen reactive T cell clones for both diseases. This will take advantage of the fact that there is an accumulation of activated T cells in the lung and that preliminary studies indicate that, utilizing T cell growth factor, the establishment of continous T cell lines is feasible in both diseases. We will attempt to develop in vitro assays for antigen-specific T cell clones with the use of antigen (beryllium salts and standardized preparation of Kveim antigens) and autologous accessory feeder cells. The long-term goal of this component of the study will be to develop an in vitro assay for the Kveim antigen and begin to identify the putative antigens that may be contained in the Kveim preparations. These investigations are part of a long-range interest in interstitial and fibrotic lung diseases and are a component of the Interstitial Lung Disease Program (and Sarcoidosis Clinic) at the Hosp. of Univ. of Pa.