MECHANISMS OF MINOR H ANTIGEN GVHD

次要 H 抗原 GVHD 的机制

• 批准号: 3145973
• 负责人: BRIAN L HAMILTON
• 金额: $ 19.08万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3145973
• 关键词: T lymphocyte; biological models; bone marrow transplantation; cell mediated cytotoxicity; cellular immunity; genetic strain; graft versus host disease; histocompatibility antigens; humoral immunity; immune response genes; immunoregulation; laboratory mouse; minor histocompatibility loci; mixed lymphocyte reaction test; neoplasm /cancer immunotherapy; radiation immunosuppression; splenectomy; thymectomy; tissue /cell culture; tissue donors

A murine model has been developed of graft-versus-host disease (GVHD) due to minor histocompatibility antigens (minor HA) in two strain combinations selected for H-2 identity and for mutual nonreactivity in MLC: C57BL/6-LP (H-2b combination) and B10.D2/nSn-BALB/c (H-2d combination). This model possesses many characteristics in common with human GVHD, including acute and chronic forms and has been used to systematically study the immune mechanisms that produce GVHD in response to minor HA. A new assay of the proliferative response to minor HA has been developed to study the role of non-CTL in the pathogenesis of minor HA-GVHD. Congenic strains of mice developed between C57BL/10, LP, and 129 mice have been used to demonstrate that multiple minor H antigenic differences must exist between donor and recipient strains for GVH to develop. Studies are in progress to evaluate the immunoregulation of cellular responses to minor HA in mice with transplants. Attempts to study the proliferative response of spleen cells from mice with GVHD to recipient strain and third party antigens led to the demonstration that these spleen cells were unable to respond to foreign antigens in mixed lymphocyte culture. Further studies demonstrated that mice with minor antigen GVHD have an acquired form of severe combined immunodeficiency and are unable to develop either cell-mediated or humoral immunity to specific antigens. The specific mechanism of this immunodeficiency is under investigation using both in vivo and in vitro techniques. Using adoptive transfer methods, we have been able to transfer minor antigen GVHD to secondary recipients. The cells that transfer GVHD are Thy-1+ and Lyt-2+. The ceIls that initiate GVHD have been further defined: the Lyt phenotype varies with the specific strain combination tested. (LB)

已经开发了移植物抗宿主病（GVHD）的小鼠模型， 两种菌株组合中的次要组织相容性抗原（次要HA） 选择H-2鉴别和MLC中的互不反应性：C57 BL/6-LP （H-2）B D2/nSn-BALB/c（H-2）D 组合）。 这 该模型具有许多与人类GVHD共同的特征，包括 急性和慢性形式，并已被用来系统地研究 产生GVHD的免疫机制响应于较小的HA。 新测定法 已经开发了对轻微HA的增殖反应的研究， 非CTL在轻度HA-GVHD发病机制中的作用。 同源株 在C57 BL/10、LP和129小鼠之间发育的小鼠已被用于 证明了多个较小的H抗原差异必须存在于 供者和受者菌株的GVH发展。 研究正在进行中， 评价小鼠中对微量HA的细胞应答的免疫调节 进行器官移植 本文试图研究小鼠脾细胞的增殖反应， 对受体株和第三方抗原的GVHD导致了这一证明 这些脾细胞无法对混合的外来抗原产生反应 淋巴细胞培养 进一步的研究表明， 抗原GVHD具有获得性形式的严重联合免疫缺陷， 不能产生细胞介导的或体液免疫， 抗原 这种免疫缺陷的具体机制是根据 使用体内和体外技术进行研究。 使用过继 转移方法，我们已经能够转移次要抗原GVHD， 二级收件人。 转移GVHD的细胞是Thy-1+和Lyt-2+。 引发GVHD的细胞已被进一步定义：Lyt表型 随测试的特定菌株组合而变化。 （LB）