ROLE OF T CELL COSTIMULATION IN PROGRESSIVE RENAL INJURY
ROLE OF T CELL COSTIMULATION IN PROGRESSIVE RENAL INJURY
T 细胞协同刺激在进行性肾损伤中的作用
批准号：
6013795
负责人：
MITRA K NADIM
金额：
$4.17万
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
项目状态：
未结题
起止时间：
1999-10-01 至
关键词：
CD28 molecule CD40 molecule T lymphocyte biological models cellular immunity chronic renal failure histocompatibility homologous transplantation immunocytochemistry inflammation laboratory rat macrophage pathologic process polymerase chain reaction renin angiotensin system transplantation immunology
中文摘要
翻译
描述抗原依赖和独立的过程都被认为是通过可能相互关联的协同作用的途径导致进行性肾移植衰竭。T淋巴细胞和巨噬细胞的浸润是慢性移植肾功能障碍的共同特征，在进展性损伤的残肾中也可见T淋巴细胞和巨噬细胞的渗出。本研究的目的是探讨细胞免疫在广泛肾切除所致肾损伤中的作用。T细胞共刺激信号抑制剂的出现为我们阐明T细胞和巨噬细胞在慢性进行性肾脏疾病发展中的作用提供了新的和高度特异的工具。本研究的目的是研究抑制CD28-B7和CD40-CD40L信号通路的作用，以确定它们在慢性进行性器官功能障碍模型中的作用。此外，我们计划在肾素-血管紧张素系统的药物抑制的背景下，研究T细胞共刺激通路在肾脏损伤发展中的作用。我们将验证这样一种假设，即阻断T细胞共刺激通路除了通过阻断肾素-血管紧张素系统提供肾脏保护外，还具有肾脏保护作用。更好地了解免疫机制在这种肾脏损伤模型中的作用，最终可能会在未来为慢性进行性肾脏和其他器官疾病患者带来更广泛的治疗选择。
英文摘要
DESCRIPTION Both antigen-dependent and independent processes are thought to contribute to progressive renal allograft failure through pathways that may interrelate synergistically. Infiltrates of T lymphocytes and macrophages, common features of kidneys with chronic renal allograft dysfunction, are also seen in the remnant kidney undergoing progressive injury The overall objectives of this proposal are to investigate the role of cell mediated immunity in the development of renal injury induced by extensive renal ablation. The availability of inhibitors of T cell co-stimulatory signals provides us with novel and highly specific tools to elucidate the role of T cells and macrophages in the development of chronic progressive renal disease. The aim of this proposal is to study the effects of inhibition of the CD28-B7 and CD40-CD40L pathways to determine their respective contributions to the development of chronic progressive organ dysfunction in this model. In addition, we plan to study the contribution of the T cell co-stimulatory pathway to the development of renal injury in the context of pharmacological inhibition of the renin-angiotensin system once injury is established. We will test the hypothesis that blockade of the T cell co- stimulatory pathways provides renal protection in addition to that provided by blockade of the renin-angiotensin system. Better understanding of the role of immune mechanisms in this model of renal injury may ultimately lead to broader therapeutic options for patients with chronic progressive renal and other organ diseases in the future.
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