OX-40 AND 4-IBB IN CD4 T CELL AND APC INTERACTIONS

CD4 T 细胞和 APC 相互作用中的 OX-40 和 4-IBB

• 批准号: 2604496
• 负责人: Michael Croft
• 金额: $ 22.99万
• 依托单位: LA JOLLA INSTITUTE FOR IMMUNOLOGY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2604496
• 关键词: B lymphocyte; CD4 molecule; antigen presentation; antigen presenting cell; apoptosis; arthritis; cell adhesion molecules; dendritic cells; disease /disorder model; genetically modified animals; helper T lymphocyte; laboratory mouse; lymphokines; protein biosynthesis; surface antigens; tissue /cell culture

DESCRIPTION (Adapted from Investigator's abstract): It is now widely accepted that recognition of peptide/MHC complexes on antigen presenting cells (APCs) is not sufficient for most aspects of CD4 T-cell function, and that additional interactions between T-cell co-receptors and APC accessory molecules are required for optimal cell growth, cytokine secretion, and induction of effector function. The majority of studies of costimulation have focused on the interactions between CD28 and B7, and CD40L and CD40, leading to the current concept that these are the critical molecules involved in T-cell responses. However, work by the investigator has shown that other receptor/ligand pairs can function as costimulators, for example LFA-1/ICAM-1. The goal of the current application is evaluation of the possibility that the Ox-40/Ox-40L and 4-1BB/4-1BBL interactions, which are expressed on T-cells and APC after activation, transduce critical costimulatory signals late in the response. In vitro experiments will explore the expression of Ox-40 and 4-1BB on naive, effector, and memory T-cells derived from TCR transgenic mice following stimulation with L cells expressing Ox-40L, 4-1BBL, B7, and/or ICAM-1, or physiological APC such as B-cells or dendritic cells. T-cell proliferation, Th1 and Th2 lymphokine production, and rescue from apoptosis will be measured. The role of the Ox-40/Ox-40L and 4-1BB/4-1BBL interactions in vivo in primary and secondary responses will be tested in normal mice and adoptive transfer recipients. Finally, the role of Ox-40/Ox-40L and 4-1BB/4-1BBL interactions in collagen-induced arthritis will be tested.

描述（改编自研究者摘要）：目前已广泛 接受肽/MHC复合物对抗原呈递的识别， 细胞（APC）不足以满足CD 4 T细胞功能的大多数方面， T细胞辅助受体和APC辅助受体之间的额外相互作用 分子是最佳细胞生长、细胞因子分泌和 效应子功能的诱导。 大多数关于共刺激的研究 已经集中在CD 28和B7，CD 40 L和CD 40之间的相互作用， 导致了目前的概念，这些是关键的分子， 参与T细胞反应。 然而，调查人员的工作表明， 其他受体/配体对可以作为共刺激因子， LFA-1/ICAM-1。 当前应用程序的目标是评估 Ox-40/Ox-40 L和4-1BB/4-1BBL相互作用的可能性， 活化后在T细胞和APC上表达， 反应后期的共刺激信号。 体外实验将 探索Ox-40和4-1BB在幼稚、效应和记忆中的表达 用L细胞刺激后源自TCR转基因小鼠的T细胞 表达Ox-40 L、4-1BBL、B7和/或ICAM-1，或生理APC， B细胞或树突细胞。 T细胞增殖，Th 1和Th 2淋巴因子 将测量产生和从细胞凋亡中的拯救。 的作用 在原发性和继发性肿瘤中，Ox-40/Ox-40 L和4-1BB/4-1BBL的体内相互作用 将在正常小鼠和过继转移受体中测试应答。 最后，研究了Ox-40/Ox-40 L和4-1BB/4-1BBL相互作用在细胞凋亡中的作用。 将测试胶原诱导的关节炎。