SELECTIVE EXPRESSION OF LYMPHOKINES IN T LYMPHOCYTES
T 淋巴细胞中淋巴细胞因子的选择性表达
基本信息
- 批准号:2671448
- 负责人:
- 金额:$ 8.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1997
- 资助国家:美国
- 起止时间:1997-04-01 至 2001-03-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Differential expression of lymphokines by CD4+ T cells plays a key role
in proper modulation of the immune response. Consequently, aberrant
control of lymphokine expression can have wide ranging impact on the
progression of many infectious diseases such as tuberculosis and HIV
as well as autoimmune diseases such as diabetes and multiple sclerosis.
Th1 cells, which secrete IFN-gamma, IL-2 and lymphotoxin, direct
delayed type hypersensitivity responses and are important in defense
against intracellular organisms. Th2 cells, which produce IL-4, direct
allergic or anti-inflammatory responses and protect against helminth
infections. Regulation of IFN-gamma, IL-2 and IL-4 occurs primarily at
the level of gene transcription, but the basis for the selective
expression of these lymphokines by the various T cell subsets remains
unclear. The overall objectives of this proposal are to define the
molecular mechanisms by which IFN-gamma and IL-4 are differentially
regulated by Th1 and Th2 CD4+ T cells and to develop an animal model
in which the biological importance of developing the polarized
population of T cells in response to infection and autoimmune disease
can be assessed. Our recent studies have defined a key regulatory
element in the IFN-gamma promoter which may contribute to the selective
expression of IFN-gamma in Th1 cells and lack of expression in Th2
cells via interaction with factors which can mediate and repress
expression and by methylation. The goal of this proposal is to use a
two pronged approach to test this hypothesis. The first approach will
utilize transient transfection of constructs containing this element
into Th1 and Th2 cells to dissect the molecular pathway involved. The
second concomitant approach will utilize in vivo promoter swapping
experiments designed to determine the physiological importance of this
element in the context of the endogenous gene and to address the role
of methylation. These studies will build upon the candidate's previous
training and allow her to gain significant new expertise in the
generation and assessment of transgenic animals and in analysis of the
complexity of the immune response in a whole animal context. These
skills are essential for her development into an independent
investigator. The sponsor's laboratory provides an ideal environment
in which to pursue the proposed experiments since mouse embryo
manipulation has been successfully utilized by this group and others
at this institution and all the tools necessary to analyze the mice are
available.
CD4+ T 细胞淋巴因子的差异表达起着关键作用
适当调节免疫反应。因此,异常
淋巴因子表达的控制可以对淋巴因子产生广泛的影响
结核病和艾滋病毒等许多传染病的进展
以及自身免疫性疾病,如糖尿病和多发性硬化症。
Th1 细胞分泌 IFN-γ、IL-2 和淋巴毒素,直接
迟发型超敏反应,对于防御很重要
对抗细胞内生物。 Th2 细胞产生 IL-4,直接
过敏或抗炎反应并预防蠕虫
感染。 IFN-γ、IL-2 和 IL-4 的调节主要发生在
基因转录水平,而是选择的基础
各种 T 细胞亚群仍表达这些淋巴因子
不清楚。该提案的总体目标是定义
IFN-γ和IL-4差异的分子机制
受 Th1 和 Th2 CD4+ T 细胞调节并开发动物模型
其中发展极化的生物学重要性
响应感染和自身免疫性疾病的 T 细胞群
可以评估。我们最近的研究定义了一个关键的监管
IFN-γ启动子中的元件可能有助于选择性
Th1 细胞中表达 IFN-γ,而 Th2 细胞中缺乏表达
细胞通过与可以介导和抑制的因子相互作用
表达和甲基化。该提案的目标是使用
两管齐下的方法来检验这一假设。第一种方法将
利用含有该元件的构建体的瞬时转染
进入 Th1 和 Th2 细胞以剖析所涉及的分子途径。这
第二种伴随方法将利用体内启动子交换
旨在确定其生理重要性的实验
在内源基因背景下的元素并解决其作用
甲基化。这些研究将建立在候选人之前的基础上
培训并让她获得重要的新专业知识
转基因动物的产生和评估以及分析
整个动物环境中免疫反应的复杂性。这些
技能对于她发展成为独立的人至关重要
研究者。申办者的实验室提供了理想的环境
从小鼠胚胎开始就进行所提出的实验
该组织和其他人已成功利用操纵
在这个机构,分析小鼠所需的所有工具都是
可用的。
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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{{ truncateString('MARIANNE T SWEETSER', 18)}}的其他基金
SELECTIVE EXPRESSION OF LYMPHOKINES IN T LYMPHOCYTES
T 淋巴细胞中淋巴细胞因子的选择性表达
- 批准号:
2002719 - 财政年份:1997
- 资助金额:
$ 8.75万 - 项目类别:
SELECTIVE EXPRESSION OF LYMPHOKINES IN T LYMPHOCYTES
T 淋巴细胞中淋巴细胞因子的选择性表达
- 批准号:
2886049 - 财政年份:1997
- 资助金额:
$ 8.75万 - 项目类别:
SELECTIVE EXPRESSION OF LYMPHOKINES IN T LYMPHOCYTES
T 淋巴细胞中淋巴细胞因子的选择性表达
- 批准号:
6169203 - 财政年份:1997
- 资助金额:
$ 8.75万 - 项目类别: