T Cell Initiated Gastric Pathology
T 细胞引发的胃病理学
基本信息
- 批准号:6573210
- 负责人:
- 金额:$ 27.55万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2003
- 资助国家:美国
- 起止时间:2003-01-10 至 2007-12-31
- 项目状态:已结题
- 来源:
- 关键词:Helicobacter T cell receptor antigens bacteria infection mechanism bacterial cytopathogenic effect bactericidal immunity cell cell interaction cell differentiation cell proliferation cytokine cytokine receptors disease /disorder model gastritis gastrointestinal epithelium gene targeting genetically modified animals helper T lymphocyte histopathology host organism interaction immunocytochemistry inflammation laboratory mouse leukocyte activation /transformation lipopolysaccharides polymerase chain reaction tissue /cell culture
项目摘要
DESCRIPTION (provided by applicant): The bacteria Helicobacter pylori is a major pathogen which, in addition to infecting over half of the world's population, is linked to gastric and duodenal ulcer disease, mucosal-associated lymphomas, and adenocarcinoma. Infection with H. pylori results in an early gastric infiltration of neutrophils, macrophages, CD4+ T cells, and B cells. These gastric infiltrates are accompanied by increased levels of gastric IFN-gamma, TNF-alpha, and IL-1 and by loss of gastric parietal cells, zymogenic cells, and dysplasia of gastric mucosal cells. Very little is known about the mechanisms by which this gastric infiltrate induces subsequent gastric epithelial pathology. A small animal model of Helicobacter infection, the H. felis mouse model, closely mimics the human disease in that severe gastric atrophy and gastric adenocarcinoma develops after infection. This model has allowed a careful analysis of the adaptive immune response to Helicobacter infection. Using a novel adoptive transfer model of disease, we have shown that it is the host CD4+ T cell response which is crucial for the development of H. felis-associated gastric pathology. This has directed our attention to the role of the CD4+ T cell, and its potential effector mechanisms, in the development of Helicobacter-associated gastric epithelial cell destruction and pathology. This grant application focuses on the hypothesis that recruitment and activation of CD4+ T cells in the stomach results in secondary non-antigen specific gastric epithelial cell alterations. These changes in epithelial cell proliferation and differentiation lead to gastric dysplasia and cancer formation. In order to elucidate this immune/ epithelial cell relationship and its sequelae, we propose to: 1) characterize the antigen recognition requirements of the CD4+ T cell critical for the development of Helicobacter-associated gastric pathology; and 2) determine the role of secreted or cell-surface products in the generation of Helicobacter-associated gastric epithelial pathology. These studies will utilize both in vivo models of disease, as well as a novel primary gastric epithelial cell culture system. The understanding of the basic mechanisms by which the host immune response to Helicobacter induces gastric epithelial pathology will lay the foundation for further studies on the regulation of the inflammatory response and the design of immunotherapies for Helicobacter infection and associated digestive diseases.
描述(申请人提供):幽门螺杆菌是一种主要的病原体,除了感染世界上一半以上的人口外,还与胃和十二指肠溃疡疾病、粘膜相关淋巴瘤和腺癌有关。幽门螺杆菌感染导致胃部早期中性粒细胞、巨噬细胞、CD4+T细胞和B细胞的浸润。这些胃浸润物伴随着胃内干扰素-γ、肿瘤坏死因子-α和白介素1水平的升高,并伴有胃壁细胞、产酶细胞的丢失和胃粘膜细胞的异型增生。目前对胃浸润性病变引起胃上皮病变的机制知之甚少。一种幽门螺杆菌感染的小动物模型--猫幽门螺杆菌小鼠模型,与人类的疾病非常相似,即严重的胃萎缩和胃腺癌在感染后发生。这个模型允许对幽门螺杆菌感染的适应性免疫反应进行仔细的分析。利用一种新的疾病过继转移模型,我们已经证明宿主的CD4+T细胞反应对H.Felis相关胃病的发生至关重要。这使得我们开始关注在幽门螺杆菌相关的胃上皮细胞破坏和病理过程中,CD4+T细胞的作用及其潜在的效应机制。这项赠款申请侧重于一种假设,即胃中CD4+T细胞的募集和激活会导致继发性非抗原特异性胃上皮细胞改变。这些上皮细胞增殖和分化的变化导致胃不典型增生和癌症的形成。为了阐明这种免疫/上皮细胞关系及其后遗症,我们建议:1)确定对幽门螺杆菌相关胃病理发展至关重要的CD4+T细胞的抗原识别要求;2)确定分泌或细胞表面产物在幽门螺杆菌相关胃上皮病理发生中的作用。这些研究将利用疾病的体内模型,以及一种新的原代胃上皮细胞培养系统。了解宿主对幽门螺杆菌的免疫应答诱导胃上皮细胞病变的基本机制,将为进一步研究幽门螺杆菌感染及相关消化系统疾病炎症反应的调控和免疫疗法的设计奠定基础。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Robinna Gail Lorenz其他文献
Robinna Gail Lorenz的其他文献
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{{ truncateString('Robinna Gail Lorenz', 18)}}的其他基金
Preparation for Graduate and Medical Education(PreGAME)Program
研究生和医学教育准备(PreGAME)计划
- 批准号:
9257456 - 财政年份:2014
- 资助金额:
$ 27.55万 - 项目类别:
Preparation for Graduate and Medical Education(PreGAME)Program
研究生和医学教育准备(PreGAME)计划
- 批准号:
8829327 - 财政年份:2014
- 资助金额:
$ 27.55万 - 项目类别:
Preparation for Graduate and Medical Education(PreGAME)Program
研究生和医学教育准备(PreGAME)计划
- 批准号:
8612197 - 财政年份:2014
- 资助金额:
$ 27.55万 - 项目类别:
EPITHELIAL AND INNATE SENSORS OF THE MICROBIOTA IN IBD
IBD 微生物群的上皮细胞和先天传感器
- 批准号:
7486782 - 财政年份:2007
- 资助金额:
$ 27.55万 - 项目类别:
EPITHELIAL AND INNATE SENSORS OF THE MICROBIOTA IN IBD
IBD 微生物群的上皮细胞和先天传感器
- 批准号:
6959577 - 财政年份:2005
- 资助金额:
$ 27.55万 - 项目类别:
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