MARROW TRANSPLANTATION: IMMUNE DYSFUNCTION IN GVH

骨髓移植：GVH 中的免疫功能障碍

• 批准号: 3179242
• 负责人: BRIAN L HAMILTON
• 金额: $ 14.43万
• 依托单位: UNIVERSITY OF WASHINGTON
• 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 1987-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3179242
• 关键词: Brucella abortus; T lymphocyte; acquired immunodeficiency; bacteriophage phi X174; bone marrow transplantation; disease /disorder model; genetic strain; graft versus host disease; histocompatibility antigens; humoral immunity; immunopharmacology; immunosuppressive; immunotherapy; minor histocompatibility loci; model design /development; monoclonal antibody; radiation immunosuppression; serology /serodiagnosis; thymus transplantation

A murine model of graft versus host disease (GVH) due to minor histocompatibility antigens has been developed to investigate the mechanisms of the immunodeficiency syndrome (IDS) which is associated with GVH (GVH-IDS). Donor and recipient strains of mice were selected for serologic identity at the H-2 major histocompatibility complex and for mutual nonreactivity in MLC. Mice with minor antigen GVH develop a profound immunodeficiency characterized by depressed cellular and humoral immunity. We propose to use this model to determine the mechanism(s) of GVH-IDS and to develop therapeutic methods to prevent and/or treat the immunodeficiency of bone marrow transplant recipients. Complementary in vivo and in vitro antigen-specific assays will be used. The first step will be to characterize the immunodeficiency associated with minor antigen GVH in our murine model. Antigens selected for these studies include H-2 alloantigens to measure cell mediated immunity, H-2 antigens and the viral neoantigen bacteriophage OX 174 to measure T-dependent humoral immunity, and TNP-brucella abortus to measure T-independent humoral immunity. Once the IDS has been characterized, we will use in vivo adoptive transfer and mixing experiments to determine whether GVH-IDS is due to the loss of an immunologic function (T help, B cells, etc.) or due to an active suppressor mechanism. In vitro and in vivo assays will be used to identify the specific cell populations which mediate suppression or which, if replaced, will correct the IDS. Based on the results of these studies we will begin to develop methods to prevent or correct the GVH-associated IDS, including thymus transplantation, low dose irradiation, immunosuppressive drugs, in vivo treatment with monoclonal antibodies, and injection of thymic-replacing factors. These experiments will, we hope, significantly contribute to the improved immunologic reconstitution of bone marrow transplant recipients. (TT)

小鼠移植物抗宿主病（GVH）模型，由于轻微 已经开发了组织相容性抗原来研究 免疫缺陷综合征（IDS）的机制， GVH（GVH-IDS）。 选择供体和受体小鼠品系， H-2主要组织相容性复合体的血清学同一性， MLC中的互不反应性。 具有次要抗原GVH的小鼠出现 以细胞和体液免疫功能低下为特征的严重免疫缺陷 免疫力 我们建议使用该模型来确定 GVH-IDS和开发预防和/或治疗GVH-IDS的治疗方法。 骨髓移植受者的免疫缺陷。 互补 将使用体内和体外抗原特异性测定。 第一步 将描述与次要抗原相关的免疫缺陷 在我们的小鼠模型中的GVH。 为这些研究选择的抗原包括H-2 同种异体抗原，以测量细胞介导的免疫，H-2抗原和病毒 新抗原噬菌体OX 174来测量T依赖性体液免疫， 和TNP-流产布鲁氏菌来测量T非依赖性体液免疫。 一旦 IDS已经被表征，我们将使用体内过继转移， 混合实验，以确定是否GVH-IDS是由于损失的一个 免疫功能（辅助T细胞、B细胞等）或者是由于活性抑制剂 机制 将使用体外和体内试验来鉴定 介导抑制的特定细胞群，或者如果被替换， 将更正IDS。 根据这些研究的结果，我们将开始 开发预防或纠正GVH相关IDS的方法，包括 胸腺移植，低剂量照射，免疫抑制剂， 用单克隆抗体进行体内治疗，并注射 胸腺替代因子 我们希望，这些实验 有助于改善骨髓的免疫重建 移植接受者 （TT）