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

描述(改编自调查者摘要)：它现在很广泛 接受了多肽/MHC复合体对抗原提呈的识别 细胞(APC)对CD4T细胞功能的大部分方面是不够的，并且 T细胞辅受体和APC附件之间的额外相互作用 分子是细胞最佳生长、细胞因子分泌和 效应器功能的诱导。共刺激作用的大部分研究 重点研究了CD28与B7、CD40L与CD40的相互作用， 导致了目前的概念，即这些是关键分子 参与T细胞反应。然而，调查人员的工作表明， 例如，其他受体/配体对可以起到共刺激分子的作用 LFA-1/ICAM-1。当前应用程序的目标是评估 Ox-40/Ox-40L和4-1BB/4-1BBL相互作用的可能性，这是 活化后在T细胞和APC上表达，转导关键 共刺激信号在反应后期。体外实验将会 探讨Ox-40和4-1BB在幼稚、效应器和记忆中的表达 L细胞刺激TcR转基因小鼠的T细胞 表达Ox-40L、4-1BBL、B7和/或ICAM-1，或生理APC，如 B细胞或树突状细胞。T细胞增殖与Th1/Th2淋巴因子 生产，以及从细胞凋亡中拯救出来将会被测量。美国政府的角色 原发和继发性OX-40/Ox-40L和4-1BB/4-1BBL在体内的相互作用 反应将在正常小鼠和领养转移接受者身上进行测试。 最后，Ox-40/Ox-40L和4-1BB/4-1BBL相互作用在 将对胶原蛋白诱导的关节炎进行测试。

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.