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: 6783177
• 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 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6783177
• 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.

为了响应Par-03-056，该提案回应了主题：＃5，疫苗开发和＃18， 功能性衰老。衰老个体的免疫反应性降低会限制其对抗传染性药物的能力，并降低旨在促进幼稚T细胞群体产生效应子和记忆细胞的疫苗的有效性。必须检查所有可能在老龄化个体中调节免疫系统的方法。我们将检查第二个信号策略对T细胞免疫反应的影响。半半细胞向效应子移动并最终向记忆细胞移动取决于在细胞表面接收两个信号：（1）T细胞抗原受体与抗原在MHC的背景下在抗原抗原呈现细胞表面的抗原特异性相互作用； （2）细胞表面蛋白传递的抗原独立的第二信号。最佳研究的第二个信号接收器是CD28，尽管几种T细胞表面蛋白可以接收第二个信号。我们最近发表了，通过ICAM-1在T细胞上通过ICAM-1刺激可以传递能够激活CD4+ T细胞的第二个信号，以假定主要是Th1子集的效应细胞的性质。到目前为止，仅通过CD28进行共刺激才能将NAFVE T细胞一直移至记忆细胞，并且其中包括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细胞移至存储单元 仅代表THL细胞。因此，只有两个电势第二信号能够记忆诱导。 ICAM-1尚未以任何能力来激活衰老个体的T细胞的能力测试，通过ICAM-1刺激可以增强衰老T细胞的响应能力。在当前的RE3提案中，我们将研究通过ICAM-1进行共刺激的能力：（1）激活从衰老个体中取的Nalve T细胞，以及（2）将Na'fve T细胞从老化个体转移到效应子，然后转移到记忆细胞。这两个目标将为我们的长期项目做好准备，这将是研究通过ICAM-1调节衰老人类和小鼠模型中免疫反应能力的刺激能力。