Control of GVHD with Retained GVT

本项目的目标是提高我们对移植物抗宿主病（GVHD）的认识， 移植物抗肿瘤（GVT）反应，以更深入地了解这些复杂的生物反应，并开发 可以应用到临床的策略。我们将利用一种新的生物发光成像策略 由此感兴趣的细胞群被荧光素酶（luc）基因标记并发光。为实现这一 最后，我们产生了独特的GFP/Luc转基因小鼠系以确保均匀的基因表达， 标记细胞群的可用性。luc* 细胞的运输和存活可以通过以下方式真实的实时跟踪： 高精度和灵敏度。我们将评估原代CD 4+和CDS* T细胞诱导GVHD的能力。 在GVHD诱导的关键事件的位置方面的细胞。我们假设移植物抗宿主病 通过淋巴细胞向关键部位的空间和时间迁移， 并上调进入GVHD靶器官所需的其他细胞表面分子， 胃肠道皮肤和肝脏将利用基于生物发光的成像来识别主要部位 GVHD诱导，以指导组织取样和通过FACS表征浸润细胞群 和免疫荧光。我们将进一步探索已知具有GVT反应性的细胞群， 有限的GVHD潜力来比较和对比这些细胞的运输和存活特征， 原代T细胞我们将重点关注细胞因子诱导的杀伤（CIK）和自然杀伤（NK）细胞的使用， 在临床试验中，两种细胞群均显示不会导致临床上显著的GVHD， 促进GVT效应。这个基础和翻译项目将提供深入了解GVHD病理生理学 并表征能够产生GVHD和GVT效应的细胞群，这些细胞群可用于临床 CIK细胞在项目1中被探索，该项目与项目1、2、4、5、7和8相互作用， 利用所有的核心。

The goals of this Project are to enhance our understanding of graft vs host disease (GVHD) and graft vs tumor (GVT) reactions to gain greater insight into these complex biological reactions and to develop strategies which may be translated to the clinic. We will utilize a novel bioluminescent imaging strategy whereby cell populations of interest are labeled with the luciferase (luc) gene and emit light. Towards this end we have generated a unique gfp/luc transgenic mouse line to ensure uniform gene expression and availability of labeled cell populations. Trafficking and survival of luc* cells can be followed in real time with high precision and sensitivity. We will evaluate the GVHD inducing capacity of primary CD4+ and CDS* T cells with respect to the location of key events in GVHD induction. We hypothesize that GVHD develops through the spatial and temporal migration of lymphocytes to key sites whereby alloreactive cells proliferate and upregulate other cell surface molecules required for entry into GVHD target organs such as the gastrointestinal tract, skin and liver. Bioluminescent based imaging will be utilized to identify the major sites of GVHD induction to direct tissue sampling and characterization of the infiltrating cell populations by FACS and immunofluorescence. We will further explore cell populations known to have GVT reactivity yet with limited GVHD potential to compare and contrast the trafficking and survival characteristics of these cells to primary T cells. We will focus on the use of cytokine induced killer (CIK) and natural killer (NK) cells since both cell populations have been shown to not result in clinically significant GVHD in clinical trials and may promote GVT effects. This basic and translational project will provide insights into GVHD pathophysiology and characterize cell populations capable of GVHD and GVT effects that could be translated to the clinic where CIK cells are being explored in Project 1, This Project interacts with Projects 1,2,4,5,7 and 8 and utilizes all of the Cores.