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人胚胎干细胞系HS293上I类人白细胞抗原分子的低表达率与抗原加工相关分子的表达水平有关。

The low rate of HLA class I molecules on the human embryonic stem cell line HS293 is associated with the APM components' expression level.

作者信息

Cabrera C M, Nieto A, Cortes J L, Montes R M, Catalina P, Cobo F, Barroso-Del-Jesus A, Concha A

机构信息

Stem Cell Bank of Andalucia (Spanish Central Node), Hospital Universitario Virgen de las Nieves, Granada, Spain.

出版信息

Cell Biol Int. 2007 Sep;31(9):1072-8. doi: 10.1016/j.cellbi.2007.03.015. Epub 2007 Mar 20.

Abstract

Human embryonic stem cells (hESCs) represent a promise for future strategies of tissue replacement. However, there are different issues that should be resolved before these cells can be used in cellular therapies; among others, the rejection of transplantable hESCs as a result of HLA incompatibility between donor cells and recipients. The hESCs exhibit a weak HLA class I expression on the cell surface, but today the responsible mechanisms are unknown. We have analyzed the level expression of HLA class I heavy chain, beta2-microglobulin (beta2-m), and antigen-processing machinery (APM) components (TAP1, TAP2, LMP2, LMP7, and Tapasin) using the HS293 hESC line by real-time quantitative RT-PCR. This analysis has revealed a low expression of beta2-m, HLA-B, and Tapasin, and an absence of expression of: TAP1, TAP2, LMP2, and LMP7 genes in the HS293 hESC line respect to the embryoid bodies (EBs) and the induced stem cells with IFNgamma (with significant differences, p<0.05). The lack or loss of HLA class I molecules due to the down-regulation of the APM components has been frequently found in tumors of different histology as specific mechanisms of immune-evasion. We described for the first time in this report that the hESCs shared similar mechanisms with respect to tumor cells responsible for the weak HLA class I expression on the cell surface.

摘要

人类胚胎干细胞(hESCs)为未来的组织替代策略带来了希望。然而,在这些细胞可用于细胞治疗之前,还有一些不同的问题需要解决;其中包括由于供体细胞与受体之间的HLA不相容性导致可移植hESCs的排斥反应。hESCs在细胞表面呈现出较弱的HLA I类表达,但目前其相关机制尚不清楚。我们通过实时定量RT-PCR分析了使用HS293 hESC系时HLA I类重链、β2-微球蛋白(β2-m)和抗原加工机制(APM)成分(TAP1、TAP2、LMP2、LMP7和塔帕辛)的表达水平。该分析显示,与胚状体(EBs)和用IFNγ诱导的干细胞相比,HS293 hESC系中β2-m、HLA-B和塔帕辛的表达较低,并且TAP1、TAP2、LMP2和LMP7基因无表达(具有显著差异,p<0.05)。由于APM成分的下调导致HLA I类分子的缺乏或缺失,在不同组织学类型的肿瘤中经常被发现是免疫逃避的特定机制。在本报告中,我们首次描述了hESCs在细胞表面HLA I类表达较弱方面与肿瘤细胞具有相似的机制。

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