NOVEL CD4+ T CELL COSTIMULATORY MOLECULE IN EAE

描述（改编自研究者摘要）：在 检查从具有EAE临床体征的大鼠中分离的细胞， 主要研究者注意到细胞表面标记物的存在 （0X 40）在CNS驻留的T细胞上。 这种抗原是TNF-R的一个成员， 家族，在大多数情况下只表达在MBP特异性T细胞上， 细胞，主要是那些已经归巢到中枢神经系统，导致 首席研究员在这个新的R 01中提出，OX 40是关键 EAE效应细胞表面分子。他的计划是评估 OX 40表达的生物学意义，使用抗OX 40试剂 确定炎症部位最近激活的T细胞， 通过它们的OX 40受体共刺激这些细胞，以鉴定OX 40 靶CNS组织内的配体，以制备免疫毒素和用途 在脱髓鞘复发性EAE模型中，表征人OX-40 在MS中的表达，最后，以表征体内意义 通过敲除这种受体的小鼠，在CD 4 T细胞上产生OX 40。 T细胞上EAE选择性标志物的鉴定是一个非常重要的方法。 考虑到免疫抑制剂的最新发展水平， MS的治疗，以及本研究中提出的特定方法 申请是合理的，及时的，在技能范围内， 这个调查员。

DESCRIPTION (Adapted from Investigator's abstract): In the course of examining cells isolated from rats with clinical signs of EAE, the principal investigator noted the presence of a cell surface marker (OX40) on CNS-resident T-cells. This antigen, a member of the TNF-R family, was for the most part exclusively expressed on MBP-specific T- cells and primarily on those that had homed to the CNS, leading the principal investigator to propose in this new R01 that OX40 is key surface molecule on EAE-effector cells. His plan is to assess the biological significance of the OX40 expression, using anti-OX40 reagents to define recently activated T-cells in the inflammatory site, to costimulate these cells via their OX40 receptor, to identify the OX40 ligand within the target CNS tissue, to prepare an immunotoxin and use it in a demyelinating relapsing EAE model, to characterize human OX-40 expression in MS, and finally, to characterize the in vivo significance of OX40 on CD4 T-cells by creating a mouse knockout for this receptor. The identification of EAE-selective markers on T-cells is a very worthwhile goal, given the state of the art in immunosuppressive therapies for MS, and the particular approach presented in this application is rational, timely, and within the scope of the skills of this investigator.