CD4 - CD8谱系定向分化：深入剖析

CD4-CD8 lineage commitment: an inside view.

作者信息

Kappes Dietmar J, He Xiao, He Xi

机构信息

Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.

出版信息

Nat Immunol. 2005 Aug;6(8):761-6. doi: 10.1038/ni1230.

DOI:10.1038/ni1230

PMID:16034433

Abstract

The mechanism of CD4-CD8 lineage commitment, which ensures the correlation between T cell receptor specificity and adoption of the T killer or T helper phenotype, has long been the subject of intense debate. Various approaches are slowly elucidating the underlying molecular pathways. Analysis of the function of T cell receptor signaling (the 'top-down' approach) supports the view that differences in signal strength and/or duration 'instruct' alternative commitment. Analysis of the transcriptional regulation of the genes encoding CD4 and CD8 (the 'bottom-up' approach) has identified critical cis-acting elements and their interacting factors. Finally, identification of the transcription factor Th-POK as a central component of the CD4 lineage-determining pathway has provided a new starting point from which to unravel this intriguing process 'from the inside out'.

摘要

CD4⁺-CD8⁺谱系定向分化的机制确保了T细胞受体特异性与T杀伤细胞或T辅助细胞表型的形成之间的关联，长期以来一直是激烈争论的主题。各种方法正在逐步阐明其潜在的分子途径。对T细胞受体信号传导功能的分析（“自上而下”方法）支持这样一种观点，即信号强度和/或持续时间的差异“指导”了不同的定向分化。对编码CD4和CD8的基因的转录调控分析（“自下而上”方法）已经确定了关键的顺式作用元件及其相互作用因子。最后，转录因子Th-POK被鉴定为CD4谱系决定途径的核心成分，这为从内部解开这一有趣过程提供了一个新的起点。