CD4⁺CD8⁺亚群中Foxp3⁺胸腺细胞的罕见发育情况。
Rare development of Foxp3+ thymocytes in the CD4+CD8+ subset.
作者信息
Lee Hyang Mi, Hsieh Chyi-Song
机构信息
Department of Internal Medicine, Division of Rheumatology, Washington University, St Louis, MO 63110, USA.
出版信息
J Immunol. 2009 Aug 15;183(4):2261-6. doi: 10.4049/jimmunol.0901304. Epub 2009 Jul 20.
Abstract
The CD4(+)CD8(+) (double positive, DP) stage of thymic development is thought to be the earliest period that generates natural Foxp3(+) regulatory T (Treg) cells important for the prevention of autoimmunity. However, we found that most Foxp3(+) DP cells identified by routine flow cytometry represent doublets comprised of Foxp3(-) DP and Foxp3(+) CD4(+)CD8(-) (CD4SP) cells. This was determined using analysis of flow cytometric height and width parameters, postsort contaminants, and thymocyte mixing studies. Temporal analysis of Treg cell development arising from bone marrow precursors in neonatal bone marrow chimeras suggested that Foxp3(+) DP cells are not a major percentage of Foxp3(+) thymocytes, and it supported the notion that most Treg cell development occurred at the immature HSA(high) CD4SP stage. Thus, these data demonstrate that the frequency of Foxp3(+) cells generated at the DP stage is much smaller than previously recognized, suggesting that additional thymocyte maturation may be required to facilitate efficient induction of Foxp3.
摘要
胸腺发育的CD4(+)CD8(+)（双阳性，DP）阶段被认为是产生对预防自身免疫至关重要的天然Foxp3(+)调节性T（Treg）细胞的最早时期。然而，我们发现通过常规流式细胞术鉴定的大多数Foxp3(+) DP细胞是由Foxp3(-) DP和Foxp3(+) CD4(+)CD8(-)（CD4SP）细胞组成的双联体。这是通过对流式细胞ometric高度和宽度参数、分选后污染物以及胸腺细胞混合研究的分析来确定的。对新生骨髓嵌合体中来自骨髓前体的Treg细胞发育的时间分析表明，Foxp3(+) DP细胞在Foxp(+)胸腺细胞中所占比例不大，这支持了大多数Treg细胞发育发生在未成熟的HSA(高) CD4SP阶段的观点。因此，这些数据表明，在DP阶段产生的Foxp3(+)细胞频率比以前认识到的要小得多，这表明可能需要额外的胸腺细胞成熟来促进Foxp3的有效诱导。
相似文献
1
Rare development of Foxp3+ thymocytes in the CD4+CD8+ subset.CD4⁺CD8⁺亚群中Foxp3⁺胸腺细胞的罕见发育情况。
J Immunol. 2009 Aug 15;183(4):2261-6. doi: 10.4049/jimmunol.0901304. Epub 2009 Jul 20.
2
The FOXP3+ subset of human CD4+CD8+ thymocytes is immature and subject to intrathymic selection.人类CD4+CD8+胸腺细胞中的FOXP3+亚群不成熟，且会经历胸腺内选择。
Immunol Cell Biol. 2008 Aug-Sep;86(6):523-9. doi: 10.1038/icb.2008.36. Epub 2008 May 27.
3
Runx3 regulates integrin alpha E/CD103 and CD4 expression during development of CD4-/CD8+ T cells.Runx3在CD4-/CD8+ T细胞发育过程中调节整合素αE/CD103和CD4的表达。
J Immunol. 2005 Aug 1;175(3):1694-705. doi: 10.4049/jimmunol.175.3.1694.
4
Foxp3 induction in human and murine thymus precedes the CD4+ CD8+ stage but requires early T-cell receptor expression.Foxp3 在人类和小鼠胸腺中的诱导发生在 CD4+ CD8+ 阶段之前，但需要早期 T 细胞受体表达。
Immunol Cell Biol. 2010 Jul;88(5):523-8. doi: 10.1038/icb.2010.4. Epub 2010 Feb 9.
5
Differentiation of human thymic regulatory T cells at the double positive stage.人胸腺调节性 T 细胞在双阳性阶段的分化。
Eur J Immunol. 2011 Dec;41(12):3604-14. doi: 10.1002/eji.201141614. Epub 2011 Oct 24.
6
Epigenetic and transcriptional analysis supports human regulatory T cell commitment at the CD4+CD8+ thymocyte stage.表观遗传学和转录组分析支持人类调节性 T 细胞在 CD4+CD8+ 胸腺细胞阶段的分化。
Cell Immunol. 2020 Jan;347:104026. doi: 10.1016/j.cellimm.2019.104026. Epub 2019 Dec 11.
7
Overexpression of the Runx3 transcription factor increases the proportion of mature thymocytes of the CD8 single-positive lineage.Runx3转录因子的过表达增加了CD8单阳性谱系成熟胸腺细胞的比例。
J Immunol. 2005 Mar 1;174(5):2627-36. doi: 10.4049/jimmunol.174.5.2627.
8
The CD4(+)CD8(+) and CD4(+) subsets of FOXP3(+) thymocytes differ in their response to growth factor deprivation or stimulation.FOXP3(+)胸腺细胞的CD4(+)CD8(+)和CD4(+)亚群对生长因子剥夺或刺激的反应不同。
Scand J Immunol. 2009 Oct;70(4):377-83. doi: 10.1111/j.1365-3083.2009.02307.x.
9
Human CD4 expression at the late single-positive stage of thymic development supports T cell maturation and peripheral export in CD4-deficient mice.人类CD4在胸腺发育晚期单阳性阶段的表达支持CD4缺陷小鼠的T细胞成熟和外周输出。
J Immunol. 2002 Oct 15;169(8):4347-53. doi: 10.4049/jimmunol.169.8.4347.
10
Restricted TCR-alpha CDR3 diversity disadvantages natural regulatory T cell development in the B6.2.16 beta-chain transgenic mouse.限制 TCR-α CDR3 多样性会损害 B6.2.16β-链转基因小鼠中天然调节性 T 细胞的发育。
J Immunol. 2010 Sep 15;185(6):3408-16. doi: 10.4049/jimmunol.1001088. Epub 2010 Aug 16.
引用本文的文献
1
Epigenetic instability and hypofunctionality of fetal Tregs allow a permissive regulatory environment for T effector memory maturation.胎儿调节性T细胞的表观遗传不稳定性和功能减退为效应性记忆T细胞成熟提供了一个宽松的调节环境。
Proc Natl Acad Sci U S A. 2025 Jul 29;122(30):e2506673122. doi: 10.1073/pnas.2506673122. Epub 2025 Jul 24.
2
T Cell Development: From T-Lineage Specification to Intrathymic Maturation.T细胞发育：从T细胞谱系特化到胸腺内成熟
Adv Exp Med Biol. 2025;1471:81-137. doi: 10.1007/978-3-031-77921-3_4.
3
How Thymocyte Deletion in the Cortex May Curtail Antigen-Specific T-Regulatory Cell Development in the Medulla.胸腺皮质中胸腺细胞的缺失可能会限制髓质中抗原特异性 T 调节细胞的发育。
Front Immunol. 2022 May 25;13:892498. doi: 10.3389/fimmu.2022.892498. eCollection 2022.
4
Regulatory T Cells: Concept, Classification, Phenotype, and Biological Characteristics.调节性T细胞：概念、分类、表型及生物学特性
Adv Exp Med Biol. 2021;1278:1-31. doi: 10.1007/978-981-15-6407-9_1.
5
An Integrated Epigenomic and Transcriptomic Map of Mouse and Human αβ T Cell Development.小鼠和人类 αβ T 细胞发育的综合表观基因组和转录组图谱。
Immunity. 2020 Dec 15;53(6):1182-1201.e8. doi: 10.1016/j.immuni.2020.10.024. Epub 2020 Nov 25.
6
Indirect presentation in the thymus limits naive and regulatory T-cell differentiation by promoting deletion of self-reactive thymocytes.胸腺中的间接呈递通过促进自身反应性胸腺细胞的删除来限制幼稚 T 细胞和调节性 T 细胞的分化。
Immunology. 2018 Jul;154(3):522-532. doi: 10.1111/imm.12904. Epub 2018 Feb 27.
7
Control of Regulatory T Cell Differentiation by the Transcription Factors Thpok and LRF.转录因子Thpok和LRF对调节性T细胞分化的调控
J Immunol. 2017 Sep 1;199(5):1716-1728. doi: 10.4049/jimmunol.1700181. Epub 2017 Jul 28.
8
Unique properties of thymic antigen-presenting cells promote epigenetic imprinting of alloantigen-specific regulatory T cells.胸腺抗原呈递细胞的独特特性促进同种异体抗原特异性调节性T细胞的表观遗传印记。
Oncotarget. 2017 May 30;8(22):35542-35557. doi: 10.18632/oncotarget.16221.
9
Guidance of regulatory T cell development by Satb1-dependent super-enhancer establishment.Satb1 依赖性超级增强子的建立对调节性 T 细胞发育的指导作用。
Nat Immunol. 2017 Feb;18(2):173-183. doi: 10.1038/ni.3646. Epub 2016 Dec 19.
10
A timeline demarcating two waves of clonal deletion and Foxp3 upregulation during thymocyte development.一条划分胸腺细胞发育过程中两波克隆清除和Foxp3上调的时间线。
Immunol Cell Biol. 2016 Apr;94(4):357-66. doi: 10.1038/icb.2015.95. Epub 2015 Oct 29.
本文引用的文献
1
Antigen-specific peripheral shaping of the natural regulatory T cell population.天然调节性T细胞群体的抗原特异性外周塑造
J Exp Med. 2008 Dec 22;205(13):3105-17. doi: 10.1084/jem.20081359. Epub 2008 Dec 8.
2
Autoantigen-specific interactions with CD4+ thymocytes control mature medullary thymic epithelial cell cellularity.与CD4+胸腺细胞的自身抗原特异性相互作用控制着成熟的髓质胸腺上皮细胞的细胞数量。
Immunity. 2008 Sep 19;29(3):451-63. doi: 10.1016/j.immuni.2008.08.007.
3
The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator.由阳性选择的胸腺细胞产生的细胞因子RANKL促进表达自身免疫调节因子的髓质胸腺上皮细胞的生长。
Immunity. 2008 Sep 19;29(3):438-50. doi: 10.1016/j.immuni.2008.06.018.
4
The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance.肿瘤坏死因子家族受体RANK和CD40协同建立胸腺髓质微环境和自身耐受性。
Immunity. 2008 Sep 19;29(3):423-37. doi: 10.1016/j.immuni.2008.06.015.
5
Differentiation of regulatory Foxp3+ T cells in the thymic cortex.胸腺皮质中调节性Foxp3+ T细胞的分化。
Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11903-8. doi: 10.1073/pnas.0801506105. Epub 2008 Aug 11.
6
A two-step process for thymic regulatory T cell development.胸腺调节性T细胞发育的两步过程。
Immunity. 2008 Jan;28(1):100-11. doi: 10.1016/j.immuni.2007.11.021.
7
Shaping of the autoreactive regulatory T cell repertoire by thymic cortical positive selection.胸腺皮质阳性选择对自身反应性调节性T细胞库的塑造
J Immunol. 2007 Nov 15;179(10):6741-8. doi: 10.4049/jimmunol.179.10.6741.
8
TCR-based lineage tracing: no evidence for conversion of conventional into regulatory T cells in response to a natural self-antigen in pancreatic islets.基于TCR的谱系追踪：没有证据表明常规T细胞会因胰腺胰岛中的天然自身抗原而转化为调节性T细胞。
J Exp Med. 2007 Sep 3;204(9):2039-45. doi: 10.1084/jem.20070822. Epub 2007 Aug 27.
9
Adaptation of TCR repertoires to self-peptides in regulatory and nonregulatory CD4+ T cells.调节性和非调节性CD4+ T细胞中TCR库对自身肽的适应性。
J Immunol. 2007 Jun 1;178(11):7032-41. doi: 10.4049/jimmunol.178.11.7032.
10
Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells.由艾里（Aire）阳性髓质胸腺上皮细胞表达和呈递的、针对自身抗原的叉头框蛋白3（Foxp3）阳性调节性T细胞的选择。
Nat Immunol. 2007 Apr;8(4):351-8. doi: 10.1038/ni1444. Epub 2007 Feb 25.
Zotero 插件