CELLULAR ENGINEERING AND IMMUNOLOGICAL AGING

细胞工程和免疫老化

• 批准号: 3116282
• 负责人: ROBERT A GOOD
• 金额: $ 11.46万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-01-01 至 1990-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3116282
• 关键词: B lymphocyte; T lymphocyte; aging; antibody formation; autoimmune disorder; bone marrow transplantation; cellular pathology; genetic manipulation; graft versus host disease; immune complex; immunogenetics; immunoregulation; leukocyte activation /transformation; major histocompatibility complex; radiation genetics; tissue /cell culture; tissue mosaicism

This project represents continuation of an effort using experimental analysis to perfect allogeneic bone marrow transplantation for treatment and prevention of diseases Clinically allogeneic bone marrow transplantation based on experimental analyses in animals has become an accepted treatment for some 50 otherwise lethal diseases. Use of marrow transplantation has shown logarithmic growth since we performed the first successful allogeneic marrow transplants using matched sibling donors more than 18 years ago. Following leads of Israeli colleagues we developed in collaboration with Resiner marrow purging approaches that used lectin agglutination and E-rosetting plus differential centrifugation to make possible HLA haploidentical transplants when HLA matched sibling donors were not available. Current investigations focus on exploring means for marrow transplantation additional to autologous, syngeneic, MHC matched allogeneic or T- cell purged MHC haploidentical donors. We developed a new model which seems to permit allogeneic marrow transplantation in mice of MHC mismatched marrow. The method depends on first tolerizing prospective donors plus purging the marrow of T cells and T precursors with anti Thy- 1 + C. We will investigate whether this model is applicable to treatment and prevention of autoimmune disease in BXSB mice and of disease in each of several other autoimmune-prone strains. We will also test this approach to prepare long term chimerism in autoimmune-resistant mice and compare crucial immunological functions in the chimeras where recipients are autoimmune-prone or autoimmunity resistant. We will determine whether bone marrow transplants from congenic resistant, allogeneic MHC matched resistant, or MHC mismatched resistant marrow donors can permit prevention or facilitate treatment of breast canter in mice. Using marrow transplants from congenic senility-resistant, HLA matched or HLA mismatched senility - resistant mice we will try to influence development of manisfestation of senility in a new senility-accelerated mutant SAM(P). We will explore bone marrow transplantation to make possible organ transplantation without continuous treatment with immunosuppressive and determine whether bone marrow transplantation can introduce mechanisms of resistance to development of atherosclerosis and coronary vascular disease in auto-immunity- prone mice. We will continue ongoing research to understand the molecular basis for B cell abnormalities in auto-immune prone mice.

该项目代表了使用 实验分析以完善同种异体骨髓 临床治疗和预防疾病的治疗和预防 基于实验的同种异体骨髓移植 动物的分析已成为大约50的公认治疗方法 否则致命疾病。 使用骨髓移植已显示 自从我们取得了第一个成功以来，对数增长 使用匹配的兄弟姐妹供体的同种异体骨髓移植更多 比18年前。 以色列同事的潜在客户 与旋转师骨髓清除方法合作开发 使用凝集素的凝集和电子缓解以及差异 离心以使HLA单倍性移植可能 HLA匹配的兄弟姐妹捐赠者没有可用。 当前的 调查重点是探索骨髓移植的手段 除了自体，同性，MHC匹配的同种异体或T- 细胞清除MHC单倍体供体。 我们开发了一个新模型 这似乎允许在小鼠的小鼠中移植 MHC不匹配的骨髓。 该方法取决于首先容忍 潜在的供体以及清除T细胞和T的骨髓 抗thy-1 + C的前体。我们将调查是否 模型适用于自身免疫的治疗和预防 BXSB小鼠的疾病和疾病的疾病 自身免疫性抗菌株。 我们还将测试这种方法 在自身免疫性小鼠中准备长期的嵌合体，然后 比较嵌合体中关键的免疫功能 接收者具有自身免疫性或自身免疫性抗性。 我们将 确定骨髓的抗性抗药性是否是 同种异体MHC匹配抗性或MHC不匹配的抗性 骨髓供体可以允许预防或促进 乳房在小鼠中。 使用来自同类的骨髓移植 抗性，HLA匹配或HLA不匹配的衰老 - 抵抗小鼠，我们将试图影响 在新的衰老加工突变体中的衰老的满足感 山姆（p）。 我们将探索骨髓移植以使 可能的器官移植，无需连续处理 免疫抑制并确定骨髓移植是否 可以引入对发展的抵抗机制 自身免疫性的动脉粥样硬化和冠状动脉血管疾病 俯卧的老鼠。 我们将继续进行研究，以了解 自身免疫易易发小鼠B细胞异常的分子基础。