MARROW TRANSPLANTATION: IMMUNE DYSFUNCTION IN GVH

小鼠移植物抗宿主病(GVH)模型的建立 已经开发了组织相容性抗原来研究 与免疫缺陷综合征相关的免疫缺陷综合征的机制 GVH(GVH-IDs)。选择供体和受体品系的小鼠用于 H-2主要组织相容性复合体的血清学鉴定 MLC中的相互无反应性。携带少量GVH抗原的小鼠会发展为 以细胞和体液抑制为特征的严重免疫缺陷 豁免权。我们建议用这个模型来确定(S)的发病机制。 GVH-IDS并开发治疗方法以预防和/或治疗 骨髓移植受者的免疫缺陷。互补输入 将使用体内和体外抗原特异性分析。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出现GVH。为这些研究选择的抗原包括H-2 用于检测细胞免疫的同种异体抗原、H-2抗原和病毒 新抗原噬菌体OX 174检测T依赖体液免疫， 和TNP-布鲁氏菌流产检测T非依赖性体液免疫。一次 已经确定了入侵检测系统的特征，我们将使用体内收养转移和 混合实验以确定GVH-IDs是否是由于 免疫功能(T细胞、B细胞等)或者由于一个主动的抑制者 机制。体外和体内试验将用于鉴定 调节抑制的特定细胞群，或者如果被取代， 将更正入侵检测系统。根据这些研究的结果，我们将开始 制定预防或纠正与GVH相关的入侵检测的方法，包括 胸腺移植，低剂量照射，免疫抑制药物，在 用单抗进行体内治疗，并注射 胸腺替代因子。我们希望，这些实验将显著地 有助于改善骨髓的免疫重建 移植受者。(TT)

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)