IMMUNOREGULATORY ROLE OF HUMAN ALVEOLAR MACROPHAGES

细胞介导的免疫反应在肺中起关键作用 肺防御和过敏性肺部疾病。抗原 在诱导阶段和诱导阶段都需要提呈细胞。 触发细胞介导的反应的效应器。 拟议研究的目标是描述有效的 人肺组织中的抗原提呈细胞(S) 调节免疫生成的细胞间相互作用 肺部的反应。我们认为位于呼吸道的DC BALT中和间质中的上皮是关键抗原 在肺中呈现细胞。此外，我们建议肺 巨噬细胞在免疫生成过程中与DC的相互作用 回应。在某些情况下，肺泡巨噬细胞(AM) 抑制性细胞；在其他情况下，它们维持或增强 DC诱导的反应。最后，我们提出了自然杀手 (NK)细胞通过抑制免疫反应的产生 对DC的细胞毒作用。 为评价DC、肺组织的相对效率 巨噬细胞和AM(来自支气管肺泡灌洗液)作为抗原 呈现细胞，我们将所有这些细胞从相同的 开始肺组织准备。六个具体目标 是：(1)制备DC富集型人群和肺组织 人肺组织巨噬细胞富集群；(2)至 研制细胞毒性DC特异性单抗；(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 通过比较他们刺激同种异体混合的能力 白细胞反应，自体混合白细胞反应， 免疫个体的二次反应和一次免疫 体外反应。此外，我们将确定AM是否 能刺激DC启动的T细胞增殖；(4)我们将 测定人血DC、人肺DC、肺 组织巨噬细胞和AM可作为辅助细胞 一次抗体形成细胞的产生；(5)是否 肺树突状细胞与单核细胞、AM和肺组织的相互作用 巨噬细胞在免疫反应调节中的作用 这些细胞改变DC诱导的T细胞增殖的能力 和抗体形成细胞生成；以及(6)NK细胞是否 通过评估辅助细胞的活性来调节其活性 NK细胞的耗尽或增加改变了刺激物的能力 产生混合白细胞反应的人群。

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.