多个发育阶段特异性增强子调控发育中的胸腺细胞和非胸腺依赖性T细胞中的CD8表达。

Multiple developmental stage-specific enhancers regulate CD8 expression in developing thymocytes and in thymus-independent T cells.

作者信息

Ellmeier W, Sunshine M J, Losos K, Littman D R

机构信息

Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University Medical Center, New York 10016, USA.

出版信息

Immunity. 1998 Oct;9(4):485-96. doi: 10.1016/s1074-7613(00)80632-9.

DOI:10.1016/s1074-7613(00)80632-9

PMID:9806635

Abstract

We and others have recently identified a CD8 locus enhancer (E8) that directs expression in mature CD8 single-positive thymocytes and peripheral CD8+ T cells and in extrathymically derived intestinal intraepithelial lymphocytes (IEL). In this study, we show that deletion of E8, by homologous recombination results in reduced CD8alphaalpha homodimer expression on IEL. Since CD8 expression on thymus-derived T cells was normal, other enhancers regulate CD8 expression in these cells. By exploiting a transgenic reporter expression assay, we identified three additional enhancers that directed expression in diverse thymocyte subsets and mature T cells but not in CD8alphaalpha+ IEL. The results suggest that CD8alpha expression is primarily regulated by E8, in IEL and by the novel enhancers in the thymus-dependent lineages.

摘要

我们和其他研究人员最近鉴定出一个CD8基因座增强子（E8），它可指导在成熟的CD8单阳性胸腺细胞、外周CD8⁺ T细胞以及胸腺外来源的肠道上皮内淋巴细胞（IEL）中表达。在本研究中，我们表明通过同源重组缺失E8会导致IEL上CD8αα同二聚体表达降低。由于胸腺来源的T细胞上的CD8表达正常，其他增强子调节这些细胞中的CD8表达。通过利用转基因报告基因表达测定法，我们鉴定出另外三个增强子，它们指导在不同的胸腺细胞亚群和成熟T细胞中表达，但在CD8αα⁺ IEL中不表达。结果表明，CD8α表达在IEL中主要受E8调节，而在胸腺依赖性谱系中受新的增强子调节。