PROGRAM PROJECT IN TRANSPLANTATION IMMUNOLOGY

移植免疫学项目

• 批准号: 3091826
• 负责人: ROBERT DAVID SCHREIBER
• 金额: $ 29.71万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 1996-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3091826
• 关键词: immunoregulation; interleukin 1; transplantation immunology; tumor necrosis factor alpha

This proposal represents the first renewal application of our program project in transplantation immunology. The original focus of this program was on (a) antigen presentation and (b) cytokine regulation of immune cell function: two specific issues of paramount importance to transplant biologists. The current proposal continues this overall focus but now concentrates on the topic of cytokine immunobiology with particular emphasis on TNF and IL-1. Project 2 follows up an observation made by Robert Schreiber, Kathleen Sheehan and Paul Lacy that TNF and IL-1 can profoundly suppress T cell activation and graft rejection responses in normal mice. Schreiber and Sheehan now propose to study the cellular and molecular basis of this immunosuppressive process by examining the effects of these cytokines on antigen presenting cell function and T cell development in vivo and in vitro. Since IL-1 holds such a prominent position in this program project, the third project will characterize the physiologic mechanism by which IL-1beta is activated. Herein, David Chaplin will perform a detailed molecular analysis on a newly defined enzyme that appears to be uniquely required for proteolytically activating murine (and human) IL-1beta. Project 3 will directly apply the principles of cytokine biology which have been and continue to be obtained from our basic research studies to models of xenograft and allograft rejection. Drs. Paul Lacy and David Scharp will expand their studies on the use of TNF, IL-1 and the combination of TGFbeta and anti-IFNgamma to suppress the rejection of pancreatic islet grafts. This project is likely to provide direct benefits to transplantation biologists by better defining the basic mechanisms involved in the induction of immunologic tolerance and by helping to develop novel and safer immunosuppressive therapeutic agents. Thus, the overall benefit of this particular program project continues to be the efficient application of basic immunologic concepts to the field of transplantation biology.

这份提案代表了我们计划的第一次更新申请 移植免疫学项目。 本节目的初衷是 是（a）抗原呈递和（B）免疫细胞的细胞因子调节 功能：移植的两个至关重要的具体问题 生物学家 目前的提案继续这一总体重点，但现在 专注于细胞因子免疫生物学的主题， 强调TNF和IL-1。 项目2是对下列人士提出的意见采取后续行动： Robert Schreiber，Kathleen Sheehan和Paul Lacy认为TNF和IL-1可以 严重抑制T细胞活化和移植排斥反应， 正常小鼠 Schreiber和Sheehan现在建议研究细胞和 这种免疫抑制过程的分子基础， 这些细胞因子对抗原呈递细胞功能和T细胞 体内和体外发育。 由于IL-1具有如此显著的 在这个项目中，第三个项目将描述 IL-1 β被激活的生理机制。 在此，大卫 卓别林将对一种新定义的 一种似乎是唯一需要蛋白水解激活的酶 鼠（和人）IL-1 β。 项目3将直接应用这些原则 细胞因子生物学，已经并将继续从我们的 异种移植和同种异体移植排斥模型的基础研究。 Drs.保罗·莱西和大卫·沙尔普将扩大他们对使用 TNF、IL-1以及TGF β和抗IFN γ的组合来抑制肿瘤细胞增殖。 胰岛移植物排斥反应。 该项目可能会提供 通过更好地定义移植生物学家的基本 参与诱导免疫耐受的机制， 有助于开发新的和更安全的免疫抑制治疗剂。 因此，这一特定计划项目的总体效益继续 将基本免疫学概念有效地应用于 移植生物学