CD8+ T cell trafficking to the normal lung

描述（由申请人提供）：本项目旨在研究CD 8 + T淋巴细胞向正常（非炎症）小鼠肺的肺微循环（肺泡毛细血管）和相关间质组织/气道的运输。 我们的长期目标是了解，在分子方面，调节活化的CD 8 + T细胞迁移到肺微循环的因素，这些细胞在该网站的保留，以及随后的细胞从血管室进入肺微循环的出口。 这是基于我们的新证据，表明活化的CD 8 + T细胞保留在正常的肺环境中，因为它们组成性地从肺循环血管室排出（即，肺泡毛细血管）进入正常/非炎症肺的肺泡。 我们的数据进一步表明，延长T细胞滞留和出口到肺结节可能介导的特异性粘附受体/配体相互作用，并可能依赖于趋化因子依赖性归巢/滞留机制。 为了进一步探索活化的CD 8 + T细胞在正常肺中归巢/滞留的过程，我们提出以下具体目的：1.描述初始（静息）和活化的CD 8 + T淋巴细胞向正常（非炎症）肺微循环的运输，以及这些细胞向肺泡微循环的流出; 2. 分析活化的CD 8 + T细胞归巢于肺微血管床并进入正常肺组织的机制。 我们将采用多种策略，包括细胞和整体动物成像技术，以检查转移的CD 8 + T细胞在正常肺内的保留和区室化。 拟议的分析应提供新的信息的因素控制T淋巴细胞与肺微循环和相关的肺/气道，以及控制这一过程的基本机制。

DESCRIPTION (provided by applicant): This project is designed to investigate the trafficking of CD8+ T-lymphocytes to the pulmonary microcirculation (alveolar capillaries) and the associated interstitial tissue/airways of the normal (noninflamed) murine lungs. Our long-term objective is to understand, in molecular terms, the factors which regulate activated CD8+ T-cell migration to the pulmonary microcirculation, the retention of those cells at the site, and the subsequent egress of the cells from the vascular compartment into the lung interstitium. It is based on our emerging evidence suggesting that activated CD8+ T-cells are retained in the normal lung environment, because they constitutively egress from the pulmonary circulation vascular compartment (i.e., alveolar capillaries) into the interstitium of the normal/non-inflamed lungs. Our data further suggests that prolonged T-cell retention and egress into the lung interstitium may be mediated by specific adhesive receptor/ligand interactions, and may be dependent on a chemokine-dependent homing/retention mechanism. To further explore this process of activated CD8+ T-cell homing/retention in the normal lungs, we propose the following Specific Aims: 1. To characterize the trafficking of naive (resting) and activated CD8+ T lymphocytes to the normal (non-inflamed) pulmonary microcirculation, and the egress of these cells into the alveolar interstitium; 2. To analyze the mechanism by which activated CD8+ T-cells home to the pulmonary micro capillary bed and egress into the interstitium of the normal lung. We will employ a variety of strategies including cell and whole animal imaging techniques to examine the retention and compartmentalization of transferred CD8+ T-cells within the normal lungs. The proposed analysis should provide new information on the factors controlling the interaction of T-lymphocytes with the pulmonary microcirculation and the associated interstitium/airways, as well as, on the underlying mechanism controlling this process.