IMMUNE FUNCTIONS OF ACCESSORY CELLS IN THE LUNG

这项拟议研究的长期目标是分析免疫 肺辅助细胞的功能及其与免疫的关系 由外来抗原引发的反应。树突状细胞(DC)是 最有效的辅助细胞，已从呼吸道上皮和 周围肺间质。呼吸道上皮中的细胞类似于 表皮朗格汉斯细胞；它们处理抗原，但不容易 刺激静息T细胞。相比之下，肺间质中的则不是。 直接处理颗粒抗原，但在体内是有效的辅助细胞 一种混合的白细胞反应。在这项提案中，实验旨在 在Lewis大鼠身上，检测呼吸道上皮细胞中DC的能力 内吞和就地加工可溶性和颗粒性抗原 确定刺激它们迁移到局部淋巴结的因素。许多 从肺血管间室分离的DC具有表型 不像一般流通中的人那样成熟。设计了实验 目的：研究人外周血树突状细胞的表型和功能。 并将其与从肺组织分离的DC进行比较 一般环流。树突状细胞对肺血管系统的交通增加 在气管内滴注和/或全身给药后 选定的细胞因子将被用于确定：A细胞因子的作用 树突状细胞对肺的趋化作用及b.ICAM-L/LFA-L介导 DC与肺内皮细胞的黏附。重要的共刺激抗原。 B7存在于肺树突状细胞的一个亚群上。研究的目的是确定在 DC，从小鼠骨髓和/或血液中培养，处于 B7在树突状细胞上的表达分化及体外鉴定 并在小鼠肺中原位实验，这些细胞因子调节其 表情。能在小鼠体内培养Ia DC前体细胞来源的DC 从血液和骨髓中，现在可以检测、利用 超薄冰冻切片细胞内免疫金标记法 MHC II类抗原、不变链和抗原所在的隔室 互动。而来自外周肺的高度纯化的间质DC 不要吞噬细菌，加入少量的间质 巨噬细胞导致DC的抗原提呈增加200%。 探讨了可能涉及的机制。制定合理的战略 为了在致敏的早期阶段控制肺免疫， 重要的是要详细了解肺损伤的机制 辅助细胞与免疫系统的其他元素相互作用，并 定义控制其功能的因素。

The long term objective of the proposed research is to analyze the immune functions of accessory cells in the lung and to relate them to immune responses triggered by foreign antigens. Dendritic cells (DC), one of the most potent accessory cells, have been isolated from airway epithelium and interstitium of peripheral lung. Those in airway epithelium resemble epidermal Langerhans cells; they process antigen, but do not readily stimulate resting T-cells. Those in lung interstitium, by contrast, do not directly process particulate antigens, but are potent accessory cells in a mixed leukocyte reaction. In this proposal, experiments are designed to examine, in the Lewis rat, the ability of DC in airway epithelium to endocytose and process soluble and particulate antigens in situ and to identify factors that stimulate their migration to local lymph nodes. Many DC isolated from the pulmonary vascular compartment are phenotypically less mature than those in the general circulation. Experiments are devised to characterize the phenotype and function of DC isolated from the pulmonary vascular compartment and compare them to DC isolated from the general circulation. The augmented traffic of DC to the lung vasculature following intra-tracheal instillation and/or systemic administration of selected cytokines will be utilized to determine the role of: a. cytokine mediated chemoattraction of DC to lungs and b. ICAM-l/LFA-l mediated adhesion of DC to lung endothelium. The important co-stimulatory antigen. B7 is present on a subset of lung DC. Studies are designed to determine in DC, cultured from mouse bone marrow and/or blood, the stage of differentiation at which B7 is expressed on DC and to identify, in vitro and in situ using mouse lung, those cytokines that regulate its expression. With the ability to culture DC from Ia DC precursors in mouse blood and from bone marrow, it is now feasible to examine, utilizing immunogold labeling on ultra-thin cryosections, the intracellular compartments in which MHC class II antigens, invariant chain and antigen interact. While highly purified interstitial DC from the peripheral lung do not phagocytose bacteria, addition of small numbers of interstitial macrophages results in a 200% increase in antigen presentation by DC. Potential mechanisms involved are explored. To develop rational strategies to control pulmonary immunity at early stages of sensitization it is important to understand in detail the mechanisms by which pulmonary accessory cells interact with other elements of the immune system and to define the factors regulating their function.