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使用HLA II类四聚体检测1型糖尿病中CD4+自身反应性T细胞。

Detection of CD4+ autoreactive T cells in T1D using HLA class II tetramers.

作者信息

Reijonen Helena, Kwok William W, Nepom Gerald T

机构信息

Benaroya Research Institute at Virginia Mason, Seattle, Washington 98101, USA.

出版信息

Ann N Y Acad Sci. 2003 Nov;1005:82-7. doi: 10.1196/annals.1288.009.

DOI:10.1196/annals.1288.009
PMID:14679042
Abstract

The use of soluble class II MHC tetramers has enabled the identification of autoantigen-specific T cells in the peripheral blood of type 1 diabetes patients. Our approach takes advantage of the appearance of highly activated T cells expressing a CD25(+)/CD4(high+) phenotype induced by immobilized class II MHC monomer containing the GAD65 peptide. Almost all T cells that stain with the specific tetramer reside in this population and, since this activation profile is not present in normal subjects, it may provide a useful tool for analysis of the T cell response in autoimmune diabetes. The utilization of tetramer techniques in the detection of autoreactive T cells is a powerful tool to gain insight into mechanisms of the molecular basis of autoimmunity. The phenotyping of T cells should provide useful markers for progression of immune-mediated beta cell reactivity and can be utilized in clinical trials to evaluate the efficacy of the immunomodulatory therapies targeting intervention/prevention of autoimmune diseases.

摘要

可溶性II类主要组织相容性复合体(MHC)四聚体的应用,使得在1型糖尿病患者外周血中鉴定自身抗原特异性T细胞成为可能。我们的方法利用了固定化的含GAD65肽的II类MHC单体诱导表达CD25(+)/CD4(high+)表型的高度活化T细胞的出现。几乎所有能用特异性四聚体染色的T细胞都存在于这一群体中,而且由于正常受试者不存在这种活化特征,它可能为分析自身免疫性糖尿病中的T细胞反应提供一个有用的工具。在检测自身反应性T细胞中利用四聚体技术是深入了解自身免疫分子基础机制的有力工具。T细胞的表型分析应为免疫介导的β细胞反应性进展提供有用的标志物,并可用于临床试验,以评估针对自身免疫性疾病干预/预防的免疫调节疗法的疗效。

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