Lineage fate and intense debate: myths, models and mechanisms of CD4-versus CD8-lineage choice

被引:348
作者
Singer, Alfred [1 ]
Adoro, Stanley [1 ]
Park, Jung-Hyun [1 ]
机构
[1] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/nri2416
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Following successful gene rearrangement at alpha beta T-cell receptor (TCR) loci, developing thymocytes express both CD4 and CD8 co-receptors and undergo a life-or-death selection event, which is known as positive selection, to identify cells that express TCRs with potentially useful ligand specificities. Positively selected thymocytes must then differentiate into either CD4(+) helper T cells or CD8(+) cytotoxic T cells, a crucial decision known as CD4/CD8-lineage choice. In this Review, we summarize recent advances in our understanding of the cellular and molecular events involved in lineage-fate decision and discuss them in the context of the major models of CD4/CD8-lineage choice.
引用
收藏
页码:788 / 801
页数:14
相关论文
共 118 条
[1]   Positive selection induces CD4 promoter and enhancer function [J].
Adlam, M ;
Duncan, DD ;
Ng, DK ;
Siu, G .
INTERNATIONAL IMMUNOLOGY, 1997, 9 (06) :877-887
[2]   Commitment issues: linking positive selection signals and lineage diversification in the thymus [J].
Aliahmad, P ;
Kaye, J .
IMMUNOLOGICAL REVIEWS, 2006, 209 :253-273
[3]   TOX provides a link between calcineurin activation and CD8 lineage commitment [J].
Aliahmad, P ;
O'Flaherty, E ;
Han, P ;
Goularte, OD ;
Wilkinson, B ;
Satake, M ;
Molkentin, JD ;
Kaye, J .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 199 (08) :1089-1099
[4]   Development of all CD4 T lineages requires nuclear factor TOX [J].
Aliahmad, Parinaz ;
Kaye, Jonathan .
JOURNAL OF EXPERIMENTAL MEDICINE, 2008, 205 (01) :245-256
[5]   Negative regulation of CD4 gene expression by a HES-1-c-Myb complex [J].
Allen, RD ;
Kim, HK ;
Sarafova, SD ;
Siu, G .
MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (09) :3071-3082
[6]   A HUMAN CD4 TRANSGENE RESCUES CD4-CD8+ CELLS IN BETA-2-MICROGLOBULIN-DEFICIENT MICE [J].
BARON, A ;
HAFEN, K ;
VONBOEHMER, H .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1994, 24 (08) :1933-1936
[7]   Asynchronous coreceptor downregulation after positive thymic selection: Prolonged maintenance of the double positive state in CD8 lineage differentiation due to sustained biosynthesis of the CD4 coreceptor [J].
Barthlott, T ;
Kohler, H ;
Eichmann, K .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 185 (02) :357-362
[8]   Negative regulation of CD8 expression via Cd8 enhancer-mediated recruitment of the zinc finger protein MAZR [J].
Bilic, I ;
Koesters, C ;
Unger, B ;
Sekimata, M ;
Hertweck, A ;
Maschek, R ;
Wilson, CB ;
Ellmeier, W .
NATURE IMMUNOLOGY, 2006, 7 (04) :392-400
[9]  
Bommhardt U, 1999, J IMMUNOL, V163, P715
[10]   CD4/CD8-lineage differentiation in the thymus: From nuclear effectors to membrane signals [J].
Bosselut, R .
NATURE REVIEWS IMMUNOLOGY, 2004, 4 (07) :529-540