Gene expression in memory CD4+T cells.

记忆 CD4 T 细胞中的基因表达。

基本信息

批准号：
7091530
负责人：
HENRY Keung WONG
金额：
$ 11.65万
依托单位：
HENRY FORD HEALTH SYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-09-20 至 2008-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7091530
关键词：
CD28 molecule T cell receptor cell differentiation clinical research cytogenetics fluorescent dye /probe gel mobility shift assay gene expression genetic regulatory element helper T lymphocyte human subject immunogenetics immunologic memory immunoregulation leukocyte activation /transformation nuclear factor kappa beta polymerase chain reaction protein tyrosine phosphatase

项目摘要

DESCRIPTION (provided by applicant): Appropriate T cell function is critical to immunity against infections, effective vaccine and tumor immunity. Dysregulation of T helper cell function, particularly the memory subset as defined by CD45RO, may be associated with diseases such as autoimmune diseases, failure of tumor surveillance and frank malignancy of T cells-cutaneous T cell lymphoma. Presently, there remains a lack of understanding in the molecular mechanisms governing memory T cells in normal function and in disease, particularly in humans. The gene of focus is CTLA-4, a co-stimulatory molecule with negative regulatory properties. This gene is induced during T cell activation, plays an important role in regulating T cell activation and affects the ability of T cells to respond to antigen. CTLA-4 binds to co-stimulatory molecules 137-1 and 137-2, and is related to CD28 structurally. In the absence of CTLA-4, there is profound immune dysregulation with uncontrolled lymphoproliferation of T cells. Their preliminary studies confirmed an increased level of CTLA-4 expression in memory T cells by approximately 7-fold. When memory CD4 T cells are stimulated, the expression of CTLA-4 shows a marked increase in comparison to naive CD4 T cells. These findings support the differential regulation of CTLA-4 expression between naive and memory T cells. Given the important role of CTLA-4 in controlling T cell function, the precise expression of CTLA-4 has critical implications in the immune response. This proposal describes experiments to investigate the regulation of CTLA-4 gene expression. Specifically, the aims will be: 1) to study the transcriptional regulation of CTLA-4 promoter, and 2) to study the regulation of CTLA-4 expression during differentiation of naive T cells to memory T cells. Understanding the mechanism regulating the differential expression of CTLA-4 may provide insights for the design of therapy to modulate CTLA-4 expression for control of immune response in inflammatory autoimmune diseases and for the development of vaccines.

描述（由申请人提供）：适当的T细胞功能对于免疫，有效的疫苗和肿瘤免疫至关重要。 T辅助细胞功能的失调，尤其是由CD45RO定义的记忆子集的失调可能与诸如自身免疫性疾病，肿瘤监测失败以及T细胞T细胞T细胞T细胞淋巴瘤坦率的疾病有关。目前，仍然缺乏对正常功能和疾病（尤其是人类）中记忆T细胞的分子机制的了解。焦点基因是CTLA-4，这是一种具有负调节特性的共刺激分子。该基因在T细胞活化过程中诱导，在调节T细胞激活中起重要作用，并影响T细胞对抗原反应的能力。 CTLA-4与共刺激分子137-1和137-2结合，在结构上与CD28有关。在没有CTLA-4的情况下，T细胞的淋巴增生不受控制。他们的初步研究证实，记忆T细胞中CTLA-4表达水平升高约7倍。当刺激记忆CD4 T细胞时，与幼稚的CD4 T细胞相比，CTLA-4的表达显示出明显的增加。这些发现支持幼稚和记忆T细胞之间CTLA-4表达的差异调节。鉴于CTLA-4在控制T细胞功能中的重要作用，CTLA-4的精确表达在免疫反应中具有关键意义。该建议描述了研究CTLA-4基因表达的调节的实验。具体而言，目的是：1）研究CTLA-4启动子的转录调控，以及2）研究在幼稚T细胞与记忆T细胞分化过程中CTLA-4表达的调节。了解调节CTLA-4差异表达的机制可以为设计治疗设计以调节CTLA-4表达的设计，以控制炎症自身免疫性疾病中的免疫反应和疫苗的发展。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Differential CTLA-4 expression in human CD4+ versus CD8+ T cells is associated with increased NFAT1 and inhibition of CD4+ proliferation.

DOI：
10.1038/gene.2013.57
发表时间：
2014-01
期刊：
GENES AND IMMUNITY
影响因子：
5
作者：
Chan, D. V.;Gibson, H. M.;Aufiero, B. M.;Wilson, A. J.;Hafner, M. S.;Mi, Q-S;Wong, H. K.
通讯作者：
Wong, H. K.

Immunobiologics in the treatment of psoriasis.

免疫生物学治疗牛皮癣。