Costimulation of aged human naive T cells through ICAM-1

通过 ICAM-1 共刺激衰老的人类初始 T 细胞

• 批准号: 6949888
• 负责人: STEPHEN H BENEDICT
• 金额: $ 7.2万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6949888
• 关键词: CD28 molecule; T lymphocyte; cell adhesion molecules; cell senescence; developmental immunology; helper T lymphocyte; human old age (65+); human subject; immunologic memory; immunosuppression; leukocyte activation /transformation; phlebotomy; tissue /cell culture

In response to PAR-03-056, this proposal responds to topics: #5, Vaccine Development and #18, Functional Senescence. Diminished immune responsiveness in aging individuals limits their ability to combat infectious agents and also decreases the effectiveness of vaccines designed to promote generation of effector and memory cells from the naive T cell population. It is imperative to examine all methods by which the immune system might be modulated in aging individuals. We will examine effects of second signal strategies on the aging T cell immune response. Movement of halve T cells to effector and ultimately to memory cells depends on receipt of two signals at the cell surface: (1) an antigen-specific interaction of the T cell antigen receptor with antigen in the context of MHC on the surface of an antigen-presenting cell; and (2) an antigen-independent second signal delivered by a cell surface protein. The best-studied 2nd signal receiver is CD28, although several T cell surface proteins can receive 2nd signals. We recently published that stimulation through ICAM-1 on a T cell can deliver a 2nd signal capable of activating the CD4+ T cell to assume properties of effector cells of primarily the Th1 subset. Thus far, only costimulation through CD28 has been shown capable of moving nafve T cells all the way to memory cells, and these include both Th1 and Th2 cells. We have just submitted a paper demonstrating that costimulation through ICAM-1 can move CD4+ nafve T cells to memory cells representing only Thl cells. Thus, only two potential 2nd signals are capable of memory induction. ICAM-1 has not been tested in any capacity for ability to activate T cells from aging individuals and it is possible that stimulation through ICAM-1 can enhance responsiveness of aging T cells. In the present Re3 proposal, we will investigate the ability of costimulation through ICAM-1: (1) to activate nalve T cells taken from aging individuals and (2) to move na'fve T cells from aging individuals to effector and then to memory cells. These two aims will prepare us for our long-term project, which will be to investigate the ability of stimulation through ICAM-1 to modulate immune responsiveness in aging humans and mouse models.

作为对PAR-03-056的回应，本提案回应了主题：#5，疫苗开发和#18， 功能性衰老。老年人的免疫反应性降低限制了他们对抗感染性病原体的能力，也降低了旨在促进从幼稚T细胞群产生效应细胞和记忆细胞的疫苗的有效性。必须检查所有可能用来调节老年个体免疫系统的方法。我们将研究第二信号策略对老化T细胞免疫反应的影响。一半的T细胞向效应器并最终到记忆细胞的移动依赖于细胞表面的两个信号的接收：(1)抗原特异性的T细胞抗原受体与抗原提呈细胞表面MHC背景下的抗原的相互作用；(2)由细胞表面蛋白传递的非抗原依赖的第二信号。研究最多的第二信号受体是CD28，尽管有几种T细胞表面蛋白可以接收第二信号。我们最近发表了通过ICAM-1对T细胞的刺激可以传递第二信号，能够激活CD4+T细胞，从而呈现主要是Th1亚群的效应细胞的特性。到目前为止，只有通过CD28的协同刺激才能将nafve T细胞一直移动到记忆细胞，包括Th1和Th2细胞。我们刚刚提交了一篇论文 证明通过ICAM-1的共刺激可以将CD4+NAFVE T细胞转移到记忆细胞 仅代表Thl细胞。因此，只有两个潜在的第二信号能够进行记忆诱导。ICAM-1还没有在任何能力上测试过是否有能力激活衰老个体的T细胞，通过ICAM-1的刺激可能会增强衰老T细胞的反应性。在目前的RE3方案中，我们将研究通过ICAM-1进行共刺激的能力：(1)激活来自老年人的原始T细胞；(2)将来自老年人的原始T细胞移动到效应器，然后移动到记忆细胞。这两个目标将使我们为我们的长期项目做好准备，该项目将调查通过ICAM-1调节衰老人类和小鼠模型免疫反应的能力。

项目成果

Choice of resident costimulatory molecule can influence cell fate in human naïve CD4+ T cell differentiation.

常驻共刺激分子的选择可以影响人类幼稚 CD4 T 细胞分化中的细胞命运。

• DOI: 10.1016/j.cellimm.2011.08.010
• 发表时间: 2011
• 期刊: Cellular immunology
• 影响因子: 4.3
• 作者: Williams,KelliM;Dotson,AbbyL;Otto,AmberR;Kohlmeier,JacobE;Benedict,StephenH
• 通讯作者: Benedict,StephenH

Deferiprone modulates in vitro responses by peripheral blood T cells from control and relapsing-remitting multiple sclerosis subjects.

去铁酮调节来自对照和复发缓解型多发性硬化症受试者的外周血 T 细胞的体外反应。

• DOI: 10.1016/j.intimp.2011.07.007
• 发表时间: 2011
• 期刊: International immunopharmacology
• 影响因子: 5.6
• 作者: Sweeney,MatthewE;Slusser,JoyceG;Lynch,SharonG;Benedict,StephenH;Garcia,SharonL;Rues,Laura;LeVine,StevenM
• 通讯作者: LeVine,StevenM