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Microchimerism and regulation in living relatedkidney transplant families

机译:生活相关肾脏移植家庭的微嵌合和调控

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摘要

Long-term harmful effects of immunosuppressive drugs and chronic rejection are a persistent impetus to establish methods to induce immunological tolerance to allografts. PCR-based studies have found evidence that humans and other placental mammals canhave prolonged extremely low levels of maternal cells as well as other non-self cells, referred to as microchimerism. The persistence of these cells suggests a mechanism for the maintenance of the regulatory T-cell (Treg) responses frequently detected in offspring to non-inherited maternal antigens. We test the hypothesis that the detection of very low copy levels of insertion/deletion (Indel) alleles consistent with non-inherited maternal genes, will correlate with immune regulation to non-inherited maternal antigens as detected by a trans-vivo Delayed-Type Hypersensitivity (fvDTH) assay in kidney transplant recipients, normal donors and their immediate biological family members. Preliminary data reported here compares qPCR amplification of rare DNAtemplates in the peripheral blood polymorphonuclear (PMN) fraction of cells, with the results of tvDTH assays for linked suppression of recall antigen responses in the presence of non-inherited maternal antigens [NIMA]. The two assays do not show a definitive correlation.
机译:免疫抑制药物的长期有害作用和慢性排斥反应是建立诱导同种异体移植免疫耐受方法的持久动力。基于PCR的研究发现,证据表明人类和其他胎盘哺乳动物可以延长极低水平的母体细胞以及其他非自身细胞的水平,这被称为微嵌合体。这些细胞的持久性提示了维持调节性T细胞(Treg)反应的机制,该调节性T细胞在后代中经常检测到对非遗传性母体抗原的反应。我们测试的假设是,与非遗传性母体基因一致的极低拷贝水平的插入/缺失(Indel)等位基因的检测,将与跨生命体迟发型超敏反应检测到的对非遗传性母体抗原的免疫调节相关(fvDTH)分析在肾移植受者,正常供体及其直系生物学家中进行。此处报道的初步数据比较了细胞外周血多形核(PMN)部分中稀有DNA模板的qPCR扩增与tvDTH测定的结果,该测定可在存在非遗传性母体抗原[NIMA]的情况下抑制召回抗原反应。两种测定没有显示明确的相关性。

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