CD4+CD25+Foxp3+ regulatory T cell formation requires more specific recognition of a self-peptide than thymocyte deletion

Cristina Cozzo Picca; Donald M. Simons; Soyoung Oh; Malinda Aitken; Olivia A. Perng; Christina Mergenthaler; Elizabeth Kropf; Jan Erikson; Andrew J. Caton

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CD4+CD25+Foxp3+ regulatory T cell formation requires more specific recognition of a self-peptide than thymocyte deletion

机译：与胸腺细胞缺失相比，CD4 + CD25 + Foxp3 +调节性T细胞的形成需要对自身肽的更特异性识别

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CD4+CD25+Foxp3+ regulatory T (Treg) cells are generated during thymocyte development and play a crucial role in preventing the immune system from attacking the body's cells and tissues. However, how the formation of these cells is directed by T-cell receptor (TCR) recognition of self-peptide:major histocompatibility complex (MHC) ligands remains poorly understood. We show that an agonist self-peptide with which a TCR is strongly reactive can induce a combination of thymocyte deletion and CD4+CD25+Foxp3+ Treg cell formation in vivo. A weakly cross-reactive partial agonist self-peptide could similarly induce thymocyte deletion, but failed to induce Treg cell formation. These studies indicate that CD4+CD25+Foxp3+ Treg cell formation can require highly stringent recognition of an agonist self-peptide by developing thymocytes. They also refine the "avidity" model of thymocyte selection by demonstrating that the quality of the signal mediated by agonist self-peptides, rather than the overall intensity of TCR signaling, can be a critical factor in directing autoreactive thymocytes to undergo CD4+CD25+Foxp3+ Treg cell formation and/or deletion during their development.

机译：CD4 + CD25 + Foxp3 +调节性T（Treg）细胞在胸腺细胞发育过程中产生，在防止免疫系统攻击人体的细胞和组织中起着至关重要的作用。但是，如何通过T细胞受体（TCR）识别自身肽：主要组织相容性复合物（MHC）配体来指导这些细胞的形成仍知之甚少。我们显示，与TCR具有强反应性的激动剂自身肽可以在体内诱导胸腺细胞缺失和CD4 + CD25 + Foxp3 + Treg细胞形成的组合。弱交叉反应的部分激动剂自肽可以类似地诱导胸腺细胞缺失，但不能诱导Treg细胞形成。这些研究表明，CD4 + CD25 + Foxp3 + Treg细胞的形成可能需要通过发育胸腺细胞来高度严格地识别激动剂自身肽。他们还证明了激动剂自身肽介导的信号质量而非TCR信号传导的整体强度可能是指导自身反应性胸腺细胞进行CD4 + CD25 +的关键因素，从而完善了胸腺细胞选择的“抗体”模型。 Foxp3 + Treg细胞在发育过程中形成和/或缺失。

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来源
《Proceedings of the National Academy of Sciences of the United States of America》 |2011年第36期|p.14890-14895|共6页
作者
Cristina Cozzo Picca; Donald M. Simons; Soyoung Oh; Malinda Aitken; Olivia A. Perng; Christina Mergenthaler; Elizabeth Kropf; Jan Erikson; Andrew J. Caton;
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作者单位

The Wistar Institute, Philadelphia, PA 19104;

The Wistar Institute, Philadelphia, PA 19104;

The Wistar Institute, Philadelphia, PA 19104;

The Wistar Institute, Philadelphia, PA 19104;

The Wistar Institute, Philadelphia, PA 19104;

The Wistar Institute, Philadelphia, PA 19104;

The Wistar Institute, Philadelphia, PA 19104;

The Wistar Institute, Philadelphia, PA 19104;

The Wistar Institute, Philadelphia, PA 19104;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种 eng
中图分类
关键词
affinity; immune regulation; specificity; tolerance; transgenic mice;

机译：亲和力免疫调节特异性公差;转基因小鼠;

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专利

1. Recognition of a specific self-peptide: self-MHC class II complex is critical for positive selection of thymocytes expressing the D10 TCR. [J] . Dao T, Blander JM, SantAngelo DB The Journal of Immunology: Official Journal of the American Association of Immunologists . 2003,第1期

机译：特定自身肽的识别：II类自身MHC复合物对于阳性选择表达D10 TCR的胸腺细胞至关重要。
2. LIGHT (a Cellular Ligand for Herpes Virus Entry Mediator and Lymphotoxin Receptor)-Mediated Thymocyte Deletion Is Dependent on the Interaction Between TCR and MHC/Self-Peptide [J] . Jing Wang, Yang-Xin Fu The journal of immunology . 2003,第8期

机译：LIGHT（疱疹病毒进入介体和淋巴毒素受体的细胞配体）介导的胸腺细胞缺失取决于TCR和MHC /自身肽之间的相互作用。
3. A novel mechanism of action for anti-thymocyte globulin: induction of CD4+CD25+Foxp3+ regulatory T cells. [J] . Lopez M, Clarkson MR, Albin M, Journal of the American Society of Nephrology: JASN . 2006,第10期

机译：抗胸腺细胞球蛋白的新作用机制：诱导CD4 + CD25 + Foxp3 +调节性T细胞。
4. A COMPARISON OF CD4+CD25+FOXP3+ T REGULATORY CELLS IN BLOOD AND LYMPH NODES OF CANINE OSTEOSARCOMA PATIENTS AND HEALTHY CONTROLS [C] . Kerry Rissetto, Kim Selting, Carolyn Henry, Annual Conference of the Veterinary Cancer Society . 2009

机译：CD4 + CD25 + FOXP3 + T调节细胞在犬骨瘤患者血液和淋巴结中的淋巴结和健康对照组
5. A single MEF-2 site Is a Major Positive Regulatory Element Required for Transcription of the Muscle-Specific Subunit of the Human Phosphoglycerate Mutase Gene in Skeletal and Cardiac Muscle Cells [D] . Nakatsuji, Yuji 1993

机译：一个MEF-2位点是骨骼肌和心肌细胞中人类磷酸甘油酸突变酶基因的肌肉特定亚基转录所需的主要正调控元件。
6. CD4+CD25+Foxp3+ regulatory T cell formation requires more specific recognition of a self-peptide than thymocyte deletion [O] . Cristina Cozzo Picca, Donald M. Simons, Soyoung Oh, 2011

机译：与胸腺细胞缺失相比CD4 + CD25 + Foxp3 +调节性T细胞的形成需要对自身肽的更特异性识别
7. CD4+CD25+Foxp3+ regulatory T cell formation requires more specific recognition of a self-peptide than thymocyte deletion [O] . Cozzo Picca, Cristina, Simons, Donald M., Oh, Soyoung, 2011

机译：与胸腺细胞缺失相比，CD4 + CD25 + Foxp3 +调节性T细胞的形成需要对自身肽的更特异性识别

CD4+CD25+Foxp3+ regulatory T cell formation requires more specific recognition of a self-peptide than thymocyte deletion

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