Gene expression in memory CD4+T cells.

记忆 CD4 T 细胞中的基因表达。

• 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
• 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

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 细胞功能对于感染免疫、有效疫苗和肿瘤免疫至关重要。 T 辅助细胞功能失调，特别是由 CD45RO 定义的记忆子集，可能与自身免疫性疾病、肿瘤监测失败和 T 细胞明显恶性肿瘤（皮肤 T 细胞淋巴瘤）等疾病有关。 目前，人们对控制记忆 T 细胞正常功能和疾病的分子机制仍然缺乏了解，特别是在人类中。重点基因是 CTLA-4，一种具有负调节特性的共刺激分子。该基因在T细胞激活过程中被诱导，在调节T细胞激活中发挥重要作用，并影响T细胞对抗原的反应能力。 CTLA-4与共刺激分子137-1和137-2结合，并且在结构上与CD28相关。在缺乏 CTLA-4 的情况下，会出现严重的免疫失调，导致 T 细胞淋巴细胞增殖不受控制。他们的初步研究证实，记忆 T 细胞中 CTLA-4 的表达水平增加了约 7 倍。 当记忆 CD4 T 细胞受到刺激时，CTLA-4 的表达与初始 CD4 T 细胞相比显着增加。 这些发现支持初始 T 细胞和记忆 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 的精确表达对免疫反应具有重要意义。 该提案描述了研究 CTLA-4 基因表达调控的实验。 具体来说，目标是：1）研究CTLA-4启动子的转录调控，2）研究幼稚T细胞分化为记忆T细胞过程中CTLA-4表达的调控。 了解调节 CTLA-4 差异表达的机制可能为设计调节 CTLA-4 表达的疗法以控制炎症性自身免疫性疾病的免疫反应和开发疫苗提供见解。

项目成果

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。

• DOI: 10.1016/j.clim.2007.01.006
• 发表时间: 2007
• 期刊: Clinical immunology (Orlando, Fla.)
• 作者: Chong,BenjaminF;Wong,HenryK
• 通讯作者: Wong,HenryK