T-cell development and the CD4-CD8 lineage decision

被引:536
作者
Germain, RN [1 ]
机构
[1] NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1038/nri798
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Cell-fate decisions are controlled typically by conserved receptors that interact with co-evolved ligands. Therefore, the lineage-specific differentiation of immature CD4(+)CD8(+) T cells into CD4(+) or CD8(+) mature T cells is unusual in that it is regulated by clonally expressed, somatically generated T-cell receptors (TCRs) of unpredictable fine specificity. Yet, each mature T cell generally retains expression of the co-receptor molecule (CD4 or CD8) that has an MHC-binding property that matches that of its TCR. Two models were proposed initially to explain this remarkable outcome - 'instruction' of lineage choice by initial signalling events or `selection' after a stochastic fate decision that limits further development to cells with coordinated TCR and co-receptor specificities. Aspects of both models now appear to be correct; mistake-prone instruction of lineage choice precedes a subsequent selection step that filters out most incorrect decisions.
引用
收藏
页码:309 / 322
页数:14
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