Behavior of regularity CD25+ CD4 T cells in vivo

体内规律性 CD25 CD4 T 细胞的行为

• 批准号: 7353359
• 负责人: ALEXANDER KHORUTS
• 金额: $ 0.83万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7353359
• 关键词: Accounting; Allografting; Animals; Antigen-Presenting Cells; Antigens; Autoimmune Diseases; Autoimmunity; Behavior; CD4 Positive T Lymphocytes; Cell Shape; Cells; Clinical Protocols; Condition; Consensus; Dendritic Cells; Development; Dissection; Experimental Models; Foundations; Goals; Human; IL2RA gene; Immune; Immune Tolerance; In Vitro; Knowledge; Laboratories; Lead; Lymphoid Tissue; Lymphopenia; Measures; Mediating; Mediator of activation protein; Mus; Numbers; Peripheral; Population; Production; Qualifying; Range; Regulation; Role; Specificity; Suppressor-Effector T-Lymphocytes; System; T-Cell Development; T-Lymphocyte; T-Lymphocyte Subsets; Testing; Training; Work; base; cytokine; improved; in vivo; novel strategies; prevent; reconstitution; research study; response; size; therapeutic target; tumor

Regulatory CD25+CD4 T cells are important mediators of immunologic tolerance and are likely to become a therapeutic target. However, their mechanisms in vivo remain largely unknown, and are the main focus of this proposal. The summary of the preliminary work described here shows that 1) we are able to purify in numbers sufficient for the proposed experiments antigen-specific regulatory CD25+CD4 T_;_.!!._ from wild-type TCR Tg mice and antigen-specific regulatory CD25+CD4 T cells expressing a single known TCR; 2) we have established two complementary in vivo systems to measure suppressive effects of CD25+CD4 T cells on responder T cells in non-lymphopenic animals; 3) we are able to simultaneously visualize the behavior and cellular interactions of antigen-specific CD25+CD4 T cells, antigen-specific responder T cells, and antigen-presenting dendritic cells; 4) CD25+CD4 T cells reduce the size of the T cell population responding to antigen and inhibit production of effector Thl and Th2 cytokines; and 5) CD25+CD4 T cells inhibit homeostatic proliferation of naive T cells in lymphopenic mice. The laboratory is now exceptionally poised to pursue the two specific aims in the proposal. In the first aim we will define the cellular mechanisms of by which CD25+CD4 T cells inhibit the antigen-specific T cell responses within the secondary lymphoid tissues. We will determine the fates of the dendritic cells presenting the antigen as well the antigen-specific CD25+CD4 T cells and responder T cells. In the second aim we will determine how CD25+CD4 T cells shape the development of the T cell compartment during immune reconstitution by homeostatic proliferation. In particular, we will test how CD25+CD4 T cells may regulate potentially auto-aggressive T cell clones under conditions of lymphopenia. Although cellular mechanisms constitute the main focus of this proposal, the experimental systems described are robust and are ideally suited for testing roles of specific molecules in CD25+CD4 T cell-mediated immune regulation.

调节性CD25+CD4 T细胞是免疫耐受的重要介质，并且可能

项目成果

A causal link between lymphopenia and autoimmunity.

• DOI: 10.1016/j.imlet.2004.10.022
• 发表时间: 2005-04-15
• 期刊: Immunology letters
• 影响因子: 4.4
• 作者: Khoruts A;Fraser JM
• 通讯作者: Fraser JM

A model of suppression of the antigen-specific CD4 T cell response by regulatory CD25+CD4 T cells in vivo.

体内调节性 CD25 CD4 T 细胞抑制抗原特异性 CD4 T 细胞反应的模型。

• DOI: 10.1093/intimm/dxh213
• 发表时间: 2005
• 期刊: International immunology.
• 作者: Thorstenson,KristenM;Herzovi,Laura;Khoruts,Alexander
• 通讯作者: Khoruts,Alexander

Regulatory CD4+CD25+Foxp3+ T cells selectively inhibit the spontaneous form of lymphopenia-induced proliferation of naive T cells.

调节性 CD4 CD25 Foxp3 T 细胞选择性抑制淋巴细胞减少诱导的初始 T 细胞的自发增殖。

• DOI: 10.4049/jimmunol.180.11.7305
• 发表时间: 2008
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Winstead,ColleenJ;Fraser,JoanneM;Khoruts,Alexander
• 通讯作者: Khoruts,Alexander