IMMUNOREGULATORY ROLE OF HUMAN ALVEOLAR MACROPHAGES

肺中的细胞介导的免疫应答在肺疾病中是关键的。 肺防御和过敏性肺病。 抗原 呈递细胞在诱导阶段和 触发细胞介导反应的效应肢。 拟议研究的目标是描述有效的 抗原呈递细胞，并研究 细胞间的相互作用，调节免疫的产生， 肺部的反应。 我们建议，DC，位于气道 上皮、BALT和淋巴结是关键抗原 肺中的呈递细胞。 此外，我们建议肺 巨噬细胞与DC相互作用， 应答 在某些情况下，肺泡巨噬细胞（AM）是 抑制细胞;在其他情况下，它们维持或增加 DC诱导反应。 最后，我们提出自然杀手 (NK)细胞抑制免疫反应的产生， 对DC的细胞毒性作用。 评价DC、肺组织的相对效率 巨噬细胞和AM（来自支气管肺泡灌洗）作为抗原 提呈细胞，我们将从相同的细胞中分离出所有这些细胞， 开始肺组织准备 六个具体目标 （1）制备DC富集的群体和肺移植物， 来自人肺组织的巨噬细胞富集群体;（2） 开发细胞毒性DC特异性单克隆抗体;（3） 比较获得的DC和组织巨噬细胞的能力 刺激抗原特异性T细胞反应 通过比较它们刺激同种异体混合 白细胞反应，自体混合白细胞反应， 免疫个体的继发反应和原发免疫 体外反应。 此外，我们还将确定AM是否 能刺激DC致敏的T细胞增殖;（4） 确定人血液DC、人肺DC、肺DC 组织巨噬细胞和AM可以作为辅助细胞， 第一抗体形成细胞的产生;（5）是否 肺DC与单核细胞、AM和肺组织相互作用 通过评估巨噬细胞在调节免疫反应中的作用 这些细胞改变DC诱导的T细胞增殖的能力 以及抗体形成细胞的产生;以及（6）NK细胞是否 调节辅助细胞的活性， NK细胞的消耗或添加改变了刺激因子的能力， 群体以产生混合白细胞应答。

Cell mediated immune responses in the lung are pivotal in pulmonary defense and in hypersensitivity lung diseases. Antigen presenting cells are required both at the inductive stage and in the triggering of the effector limb of cell mediated responses. The goal of the proposed studies is to characterize the effective antigen presenting cell(s) in human lung and to investigate the cell-cell interactions which regulate the generation of immune responses in the lung. We propose that DC, located in airway epithelium, in BALT and in the interstitium are critical antigen presenting cells in the lung. Further, we propose that pulmonary macrophages interact with DC during the generation of immune responses. In some instances alveolar macrophages (AM) are suppressive cells; in other instances, they maintain or augment DC induced responses. Finally, we propose that natural killer (NK) cells suppress the generation of immune responses via a cytotoxic effect on DC. To evaluate the relative efficiency of DC, lung tissue macrophages and AM (from bronchoalveolar lavage) as antigen presenting cells, we will isolate all of these cells from the same starting pulmonary tissue preparation. The six specific objectives are: (1) To prepare a DC enriched population and a pulmonary macrophage enriched population from human lung tissue; (2) To develop a cytotoxic DC specific monoclonal antibody; (3) To compare the capacity of DC and tissue macrophages obtained from human lungs to stimulate antigen specific T cell responses by comparing their ability to stimulate allogeneic mixed leucocyte responses, autologous mixed leucocyte responses, secondary responses in immune individuals and primary immune responses in vitro. Additionally, we will determine whether AM can stimulate proliferation of T cell primed by DC; (4) We will determine whether human blood DC, human pulmonary DC, lung tissue macrophages and AM can serve as accessory cells for the generation of primary antibody forming cells; (5) Whether pulmonary DC interact with monocytes, AM, and lung tissue macrophages in the regulation of immune responses by evaluating the ability of these cells to alter DC induced T cell proliferation and antibody forming cell generation; and (6) Whether NK cells regulate the activity of accessory cells by evaluating whether depletion or addition of NK cells alters the ability of stimulator populations to generate a mixed leucocyte response.