DONOR BONE MARROW AND TRANSPLANT T AND B CELL REGULATION

供体骨髓和移植 T 细胞和 B 细胞的调节

• 批准号: 6177277
• 负责人: Joshua Miller
• 金额: $ 24.45万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6177277
• 关键词: B lymphocyte; MHC class I antigen; T lymphocyte; artificial immunosuppression; biomarker; blood donor; bone marrow; bone marrow transplantation; clinical research; cytokine; gene expression; genotype; hematopoietic stem cells; hematopoietic tissue transplantation; human subject; kidney transplantation; lymph nodes; messenger RNA; outcomes research; phenotype; polymerase chain reaction; spleen; tissue mosaicism

DESCRIPTION: (Adapted from the applicant's abstract) The overall aim of this project is characterization of the presence, distribution, and function of donor derived hematopoietic cells in recipients of first cadaveric kidney transplants that are accompanied by the simultaneous administration of donor bone marrow cells. The approach will utilize a new and sensitive analytic tool developed in the laboratory, the PCR-Flow assay, that identifies the genotype and selected cell surface markers on individual cells. Preliminary evidence in 45 patients 3 to 26 months after transplantation, compared with 120 controls transplanted without donor bone marrow, shows that marrow infused patients have both a state of microchimerism and a non-specific state of immunosuppression. The proposal is to enlarge the study to 125 marrow treated patients and 250 controls, in order to relate the presence of donor cells of particular phenotype and function to clinical status, and to determine which patients may have immunosuppression discontinued. Studies will continue on the cells freshly obtained from cadaveric donors, comparing MLC and CML responsiveness and regulatory capability of subsets of bone marrow, spleen and lymph node. After transplantation, peripheral blood cells, bone marrow, and peripheral lymph nodes of recipients will be sampled at intervals for functional and phenotypic study of subsets, including expression of cytokine mRNA and protein. Results will be correlated with levels and character of chimerism found with several clinical parameters, including the presence of antibodies to HLA and transplant biopsies.

描述：（改编自申请人的摘要）的总体目标 这个项目是表征的存在，分布和功能， 供体来源的造血细胞在第一个尸体肾受体中的表达 同时给予供体的移植 骨髓细胞 该方法将利用一种新的敏感的分析方法， 在实验室中开发的工具，PCR-Flow测定， 基因型和选择的细胞表面标志物。 初步 45例患者在移植后3至26个月的证据， 120例未移植供体骨髓的对照组，显示骨髓 输注的患者具有微嵌合状态和非特异性嵌合状态。 免疫抑制状态。 建议将研究扩大到125个 骨髓治疗的患者和250名对照者，以将 特定表型和功能的供体细胞与临床状态的关系，以及 确定哪些患者可以停止免疫抑制。 研究 将继续从尸体供体新鲜获得的细胞，比较 MLC和CML的反应性和骨亚群的调节能力 骨髓、脾脏和淋巴结。 移植后，外周血 将对受者的细胞、骨髓和外周淋巴结进行取样 每隔一段时间进行子集的功能和表型研究，包括 细胞因子mRNA和蛋白的表达。 结果将与 用几个临床参数发现的嵌合体水平和特征， 包括HLA抗体和移植活检的存在。