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: 2404265
• 负责人: Joshua Miller
• 金额: $ 23.5万
• 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/2404265
• 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）总体目标 该项目描述了存在、分布和功能 第一个尸体肾脏受者体内的供体来源的造血细胞 同时给予供体的移植 骨髓细胞。 该方法将利用一种新的、灵敏的分析方法 实验室开发的工具 PCR-Flow 检测可识别 单个细胞的基因型和选定的细胞表面标记。 初步的 移植后 3 至 26 个月的 45 名患者的证据，与 120 名对照者在没有供体骨髓的情况下移植，表明骨髓 输注患者同时具有微嵌合状态和非特异性状态 免疫抑制状态。 建议将研究范围扩大到 125 骨髓治疗的患者和 250 名对照者，以便将存在的情况联系起来 特定表型和功能的供体细胞达到临床状态，并 确定哪些患者可能已停止免疫抑制。 研究 将继续使用从尸体捐献者新鲜获得的细胞，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采样 每隔一段时间对子集进行功能和表型研究，包括 细胞因子 mRNA 和蛋白的表达。 结果将与 通过几个临床参数发现嵌合体的水平和特征， 包括 HLA 抗体的存在和移植活检。