FACTORS CONTROLLING GRAFT-HOST INTERACTIONS

控制移植物-宿主相互作用的因素

• 批准号: 3225189
• 负责人: ICHIRO NAKAMURA
• 金额: $ 19.1万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-05-01 至 1992-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3225189
• 关键词: bone marrow transplantation; cell cell interaction; cell mediated lymphocytolysis test; cellular immunity; clone cells; gene expression; glycosylation; graft versus host disease; hematopoiesis; hematopoietic stem cells; histocompatibility; histocompatibility antigens; homologous transplantation; hybridomas; immunogenetics; immunoregulation; laboratory mouse; lectin; major histocompatibility complex; natural killer cells; neoplastic cell culture for noncancer research; oligosaccharides; radioimmunoassay; radiotracer; surface antigens; tissue /cell culture

Natural resistance to hemopoietic allografts, in particular F1 hybrid resistance to parental grafts, represents one of the most puzzling immunological phenomena. The resistance is genetically specific, characterized by a noncodominant mode of inheritance, and major histocompatibility complex (MHC)-controlled. The effector mechanism is mediated by natural killer (NK) cells, and hence radio-resistant and preexisting. These properties are unique, and not easily reconciled with the contemporary concepts of cellular immunology and transplantation genetics. The long- term objective of this research project is to elucidate the immunogenetic, cellular, and ultimately molecular mechanisms underlying the natural resistance. This application proposes an approach towards a molecular understanding of the cell surface target structures that are recognized in F1 hybrid resistance to parental H-2b/Hh-1b hemopoietic grafts. Studies are designed primarily to test the hypothesis that the target structures for hybid resistance are oligosaccharides. Clones of lymphoma cells lacking these determinants will be selected 1) specifically by resistant F1 hybrid hosts in vivo and 2) nonspecifically in vitro by selecting variants with altered cell surface oligosaccharides. Somatic cell hybridization will be used to study the nature of genetic lesions in the variant clones. The effect of selected glycosylation inhibitors on the expression of Hh-1b determinants will be tested and Hh-1b positive and negative clones biochemically compared. These studies are essential for a better understanding of the role of NK cells in normal hemopoiesis, in immune surveillance for hemopoietic neoplasms, and in bone marrow allograft failure in man.

对造血异体移植物的天然抗性，特别是F1