MECHANISMS OF MINOR H ANTIGEN GVHD

次要 H 抗原 GVHD 的机制

• 批准号: 3145971
• 负责人: BRIAN L HAMILTON
• 金额: $ 18.33万
• 依托单位: CHILDREN'S HOSPITAL & RES CTR AT OAKLAND
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3145971
• 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)

一种移植物抗宿主病(GVHD)的小鼠模型已经建立起来 对两个菌株组合中的次要组织相容性抗原(次要HA) 在MLC中选择H-2同一性和相互无反应性：C57BL/6-LP (H-2b组合)和B10.D2/NSN-BALB/c(H-2d组合)。这 模型具有许多与人类GVHD相同的特征，包括 急性和慢性形式，已被用来系统地研究 轻微HA引起移植物抗宿主病的免疫机制。一种新的化验方法 对微小HA的增殖反应的研究已经发展到研究 非CTL在轻度HA-GVHD发病机制中的作用猪瘟病毒同基因株 在C57BL/10、LP和129小鼠之间培育的小鼠已经习惯于 证明多个微小的H抗原差异必须存在于 供体和受体菌株为生殖器疱疹病毒的发展。研究正在进行中，以 评价小鼠对微量透明质酸细胞免疫应答的调节作用 通过移植。 小鼠脾细胞增殖反应的实验研究 GVHD对受体菌株和第三方抗原的演示 这些脾细胞不能对混合中的外来抗原产生反应 淋巴细胞培养。进一步的研究表明，患有微小疾病的小鼠 抗原GVHD具有获得性形式的严重联合免疫缺陷和 既不能产生细胞免疫，也不能产生对特定的体液免疫 抗原。这种免疫缺陷的具体机制是 使用体内和体外技术进行研究。使用领养 转移方法，我们已经能够将次要抗原GVHD转移到 第二收件人。转移GVHD的细胞为Thy-1+和Lyt-2+。 启动GVHD的细胞有了进一步的定义：Lyt表型 随测试的特定菌株组合而异。(磅)

项目成果

Suppression of B-cell development as a result of selective expansion of donor T cells during the minor H antigen graft-versus-host reaction.

在次要 H 抗原移植物抗宿主反应过程中，供体 T 细胞选择性扩增，从而抑制 B 细胞发育。

• 发表时间: 1993
• 期刊: Blood
• 影响因子: 20.3
• 作者: Garvy,BA;Elia,JM;Hamilton,BL;Riley,RL
• 通讯作者: Riley,RL

L3T4-positive T cells participate in the induction of graft-vs-host disease in response to minor histocompatibility antigens.

• DOI: 10.4049/jimmunol.139.8.2511
• 发表时间: 1987-10
• 期刊: Journal of immunology
• 影响因子: 4.4
• 作者: B. Hamilton

Immune dysfunction associated with graft-versus-host reaction in mice transplanted across minor histocompatibility barriers. I. Depressed antigen-specific antibody responses to bacteriophage phi chi 174.

跨越较小组织相容性障碍移植的小鼠中与移植物抗宿主反应相关的免疫功能障碍。

• DOI: 10.1097/00007890-198906000-00029
• 发表时间: 1989
• 期刊: Transplantation
• 影响因子: 6.2
• 作者: Hamilton,BL;Ochs,HD
• 通讯作者: Ochs,HD

Reduction of lethal graft-versus-host disease: transplantation of cultured murine bone marrow across minor histocompatibility differences

减少致命的移植物抗宿主病：跨越微小组织相容性差异的培养小鼠骨髓移植

• 发表时间: 1985
• 作者: P. Mauch;J. Lipton;B. Hamilton;J. Obbagy;D. Nathan;S. Hellman
• 通讯作者: S. Hellman

Immune dysfunction associated with graft-vs-host reaction in mice transplanted across minor histocompatibility barriers. II. Reversible defect in T-dependent antibody responses.

跨越较小组织相容性障碍移植的小鼠中与移植物抗宿主反应相关的免疫功能障碍。

• 发表时间: 1989
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Budhecha,S;Hamilton,BL
• 通讯作者: Hamilton,BL