DONOR BONE MARROW AND TRANSPLANT T AND B CELL REGULATION

描述：(改编自申请人的摘要)总体目标 这个项目是对存在、分布和功能的表征 第一例身体肾移植受者供体来源的造血细胞 供体同时给药的移植 骨髓细胞。该方法将利用一种新的、敏感的分析 在实验室开发的工具，聚合酶链式反应-流动分析，它识别 单个细胞上的基因型和选定的细胞表面标记。初步 45名患者在移植后3至26个月的证据，与 120名对照移植无供体骨髓，显示骨髓 输血患者既有微嵌合体状态，也有非特异性 免疫抑制状态。这项建议是将研究扩大到125项 骨髓治疗的患者和250名对照，以联系存在 特定表型和功能的供体细胞与临床状态和 确定哪些患者可能已停止免疫抑制。研究 将继续从身体捐赠者新鲜获得的细胞上进行比较 MLC和CML对骨细胞亚群的反应性和调节能力 骨髓、脾和淋巴结。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， 包括人类白细胞抗原抗体的存在和移植活检。

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.