谱系命运与激烈争论：CD4 与 CD8 谱系选择的神话、模型及机制
Lineage fate and intense debate: myths, models and mechanisms of CD4- versus CD8-lineage choice.
作者信息
Singer Alfred, Adoro Stanley, Park Jung-Hyun
机构信息
Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA.
出版信息
Nat Rev Immunol. 2008 Oct;8(10):788-801. doi: 10.1038/nri2416.
Abstract
Following successful gene rearrangement at alphabeta 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.
摘要
在αβ T细胞受体（TCR）基因座成功进行基因重排后，发育中的胸腺细胞同时表达CD4和CD8共受体，并经历一个生死抉择的选择事件，即阳性选择，以识别表达具有潜在有用配体特异性的TCR的细胞。然后，经过阳性选择的胸腺细胞必须分化为CD4(+)辅助性T细胞或CD8(+)细胞毒性T细胞，这一关键决定被称为CD4/CD8谱系选择。在本综述中，我们总结了我们对谱系命运决定所涉及的细胞和分子事件的理解的最新进展，并在CD4/CD8谱系选择的主要模型背景下进行讨论。
相似文献
1
Lineage fate and intense debate: myths, models and mechanisms of CD4- versus CD8-lineage choice.
Nat Rev Immunol. 2008 Oct;8(10):788-801. doi: 10.1038/nri2416.
2
The duration of antigen receptor signalling determines CD4+ versus CD8+ T-cell lineage fate.
Nature. 2000 Mar 30;404(6777):506-10. doi: 10.1038/35006664.
3
A Fateful Decision in the Thymus Controlled by the Transcription Factor ThPOK.
J Immunol. 2021 May 1;206(9):1981-1982. doi: 10.4049/jimmunol.2100157.
4
Identification of lineage-specifying cytokines that signal all CD8-cytotoxic-lineage-fate 'decisions' in the thymus.
Nat Immunol. 2017 Nov;18(11):1218-1227. doi: 10.1038/ni.3847. Epub 2017 Sep 25.
5
Transcriptional and epigenetic regulation of CD4/CD8 lineage choice.
Adv Immunol. 2011;110:71-110. doi: 10.1016/B978-0-12-387663-8.00003-X.
6
CCR7 expression in developing thymocytes is linked to the CD4 versus CD8 lineage decision.
J Immunol. 2007 Dec 1;179(11):7358-64. doi: 10.4049/jimmunol.179.11.7358.
7
The order and logic of CD4 versus CD8 lineage choice and differentiation in mouse thymus.
Nat Commun. 2021 Jan 4;12(1):99. doi: 10.1038/s41467-020-20306-w.
8
9
The zinc finger transcription factor Th-POK regulates CD4 versus CD8 T-cell lineage commitment.
Nature. 2005 Feb 24;433(7028):826-33. doi: 10.1038/nature03338.
10
Ikaros null mice display defects in T cell selection and CD4 versus CD8 lineage decisions.
J Immunol. 2004 Oct 1;173(7):4470-8. doi: 10.4049/jimmunol.173.7.4470.
引用本文的文献
1
Integrin CD103 reveals a distinct developmental pathway of autoreactive thymocytes in TCR transgenic mice.
Nat Commun. 2025 Jul 18;16(1):6627. doi: 10.1038/s41467-025-61922-8.
2
Pluripotent stem cell-based immunotherapy: advances in translational research, cell differentiation, and gene modifications.
Life Med. 2025 Jan 18;4(1):lnaf002. doi: 10.1093/lifemedi/lnaf002. eCollection 2025 Feb.
3
T Cell Development: From T-Lineage Specification to Intrathymic Maturation.
Adv Exp Med Biol. 2025;1471:81-137. doi: 10.1007/978-3-031-77921-3_4.
4
A conserved element in the first intron of has a lineage specific, TCR signal-responsive, canonical enhancer function that matches the timing of cell surface CD4 upregulation required to prevent lineage choice error.
Front Immunol. 2025 Jan 15;15:1469402. doi: 10.3389/fimmu.2024.1469402. eCollection 2024.
5
Personalized, autologous neoantigen-specific T cell therapy in metastatic melanoma: a phase 1 trial.
Nat Med. 2025 Mar;31(3):881-893. doi: 10.1038/s41591-024-03418-4. Epub 2025 Jan 3.
6
Optimizing CD8 T cell-based immunotherapy via metabolic interventions: a comprehensive review of intrinsic and extrinsic modulators.
Exp Hematol Oncol. 2024 Oct 22;13(1):103. doi: 10.1186/s40164-024-00575-7.
7
Human TCR repertoire in cancer.
Cancer Med. 2024 Sep;13(17):e70164. doi: 10.1002/cam4.70164.
8
The partitioning of TCR repertoires by thymic selection.
J Exp Med. 2024 Oct 7;221(10). doi: 10.1084/jem.20230897. Epub 2024 Aug 21.
9
Adjusting to self in the thymus: CD4 versus CD8 lineage commitment and regulatory T cell development.
J Exp Med. 2024 Oct 7;221(10). doi: 10.1084/jem.20230896. Epub 2024 Jul 9.
10
Lrp10 suppresses IL7R limiting CD8 T cell homeostatic expansion and anti-tumor immunity.
EMBO Rep. 2024 Aug;25(8):3601-3626. doi: 10.1038/s44319-024-00191-w. Epub 2024 Jul 2.
本文引用的文献
1
Scalable signaling mediated by T cell antigen receptor-CD3 ITAMs ensures effective negative selection and prevents autoimmunity.
Nat Immunol. 2008 Jun;9(6):658-66. doi: 10.1038/ni.1611. Epub 2008 May 11.
2
CD4-CD8 lineage commitment is regulated by a silencer element at the ThPOK transcription-factor locus.
Immunity. 2008 Mar;28(3):346-58. doi: 10.1016/j.immuni.2008.02.006.
3
Thymus lineage commitment: a single switch.
Immunity. 2008 Mar;28(3):297-9. doi: 10.1016/j.immuni.2008.02.011.
4
Nucleoprotein structure of the CD4 locus: implications for the mechanisms underlying CD4 regulation during T cell development.
Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3873-8. doi: 10.1073/pnas.0800810105. Epub 2008 Mar 5.
5
Repression of the transcription factor Th-POK by Runx complexes in cytotoxic T cell development.
Science. 2008 Feb 8;319(5864):822-5. doi: 10.1126/science.1151844.
6
Development of all CD4 T lineages requires nuclear factor TOX.
J Exp Med. 2008 Jan 21;205(1):245-56. doi: 10.1084/jem.20071944. Epub 2008 Jan 14.
7
IL-7 promotes Glut1 trafficking and glucose uptake via STAT5-mediated activation of Akt to support T-cell survival.
Blood. 2008 Feb 15;111(4):2101-11. doi: 10.1182/blood-2007-06-096297. Epub 2007 Nov 27.
8
Deletion of CD4 and CD8 coreceptors permits generation of alphabetaT cells that recognize antigens independently of the MHC.
Immunity. 2007 Nov;27(5):735-50. doi: 10.1016/j.immuni.2007.10.007.
9
Antagonistic interactions between Ikaros and the chromatin remodeler Mi-2beta determine silencer activity and Cd4 gene expression.
Immunity. 2007 Nov;27(5):723-34. doi: 10.1016/j.immuni.2007.09.008. Epub 2007 Nov 1.
10
The transcription factor Zbtb7b promotes CD4 expression by antagonizing Runx-mediated activation of the CD4 silencer.
J Immunol. 2007 Oct 1;179(7):4405-14. doi: 10.4049/jimmunol.179.7.4405.
Zotero 插件