将过继性调节性T细胞转移与骨髓移植相结合以实现移植耐受。
Combining Adoptive Treg Transfer with Bone Marrow Transplantation for Transplantation Tolerance.
作者信息
Pilat Nina, Granofszky Nicolas, Wekerle Thomas
机构信息
Section of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
出版信息
Curr Transplant Rep. 2017;4(4):253-261. doi: 10.1007/s40472-017-0164-7. Epub 2017 Nov 4.
Abstract
PURPOSE OF REVIEW
The mixed chimerism approach is an exceptionally potent strategy for the induction of donor-specific tolerance in organ transplantation and so far the only one that was demonstrated to work in the clinical setting. Regulatory T cells (Tregs) have been shown to improve chimerism induction in experimental animal models. This review summarizes the development of innovative BMT protocols using therapeutic Treg transfer for tolerance induction.
RECENT FINDINGS
Treg cell therapy promotes BM engraftment in reduced conditioning protocols in both, mice and non-human primates. In mice, transfer of polyclonal recipient Tregs was sufficient to substitute cytotoxic recipient conditioning. Treg therapy prevented chronic rejection of skin and heart allografts related to tissue-specific antigen disparities, in part by promoting intragraft Treg accumulation.
SUMMARY
Adoptive Treg transfer is remarkably effective in facilitating BM engraftment in reduced-intensity protocols in mice and non-human primates. Furthermore, it promotes regulatory mechanisms that prevent chronic rejection.
摘要
综述目的
混合嵌合体方法是诱导器官移植中供体特异性耐受的一种极其有效的策略，也是迄今为止唯一在临床环境中被证明有效的方法。调节性T细胞（Tregs）已被证明可改善实验动物模型中的嵌合体诱导。本综述总结了使用治疗性Treg转移诱导耐受的创新骨髓移植方案的进展。
最新发现
Treg细胞疗法在小鼠和非人灵长类动物的低强度预处理方案中促进骨髓植入。在小鼠中，多克隆受体Tregs的转移足以替代细胞毒性受体预处理。Treg疗法部分通过促进移植内Treg积累，预防了与组织特异性抗原差异相关的皮肤和心脏同种异体移植的慢性排斥反应。
总结
过继性Treg转移在促进小鼠和非人灵长类动物低强度方案中的骨髓植入方面非常有效。此外，它还促进了预防慢性排斥反应的调节机制。
相似文献
1
Combining Adoptive Treg Transfer with Bone Marrow Transplantation for Transplantation Tolerance.将过继性调节性T细胞转移与骨髓移植相结合以实现移植耐受。
Curr Transplant Rep. 2017;4(4):253-261. doi: 10.1007/s40472-017-0164-7. Epub 2017 Nov 4.
2
T-regulatory cell treatment prevents chronic rejection of heart allografts in a murine mixed chimerism model.调节性 T 细胞治疗可预防嵌合鼠模型中心脏同种异体移植物的慢性排斥反应。
J Heart Lung Transplant. 2014 Apr;33(4):429-37. doi: 10.1016/j.healun.2013.11.004. Epub 2013 Nov 28.
3
Therapeutic efficacy of polyclonal tregs does not require rapamycin in a low-dose irradiation bone marrow transplantation model.多克隆 Tregs 的治疗效果在低剂量照射骨髓移植模型中并不需要雷帕霉素。
Transplantation. 2011 Aug 15;92(3):280-8. doi: 10.1097/TP.0b013e3182241133.
4
Combining Treg Therapy With Donor Bone Marrow Transplantation: Experimental Progress and Clinical Perspective.联合调节性 T 细胞治疗与供者骨髓移植：实验进展与临床展望。
Transplantation. 2024 May 1;108(5):1100-1108. doi: 10.1097/TP.0000000000004814. Epub 2023 Oct 4.
5
Mechanistic and therapeutic role of regulatory T cells in tolerance through mixed chimerism.调节性 T 细胞在混合嵌合体诱导免疫耐受中的作用机制和治疗作用。
Curr Opin Organ Transplant. 2010 Dec;15(6):725-30. doi: 10.1097/MOT.0b013e3283401755.
6
IL-2/α-IL-2 Complex Treatment Cannot Be Substituted for the Adoptive Transfer of Regulatory T cells to Promote Bone Marrow Engraftment.白细胞介素-2/α-白细胞介素-2复合物治疗不能替代调节性T细胞的过继转移来促进骨髓植入。
PLoS One. 2016 Jan 5;11(1):e0146245. doi: 10.1371/journal.pone.0146245. eCollection 2016.
7
Treg-therapy allows mixed chimerism and transplantation tolerance without cytoreductive conditioning.Treg-疗法可在不进行细胞减少性调理的情况下实现混合嵌合和移植耐受。
Am J Transplant. 2010 Apr;10(4):751-762. doi: 10.1111/j.1600-6143.2010.03018.x. Epub 2010 Feb 10.
8
Polyclonal Recipient nTregs Are Superior to Donor or Third-Party Tregs in the Induction of Transplantation Tolerance.多克隆受体 nTregs 在诱导移植耐受方面优于供体或第三方 Tregs。
J Immunol Res. 2015;2015:562935. doi: 10.1155/2015/562935. Epub 2015 Jul 27.
9
Mixed chimerism through donor bone marrow transplantation: a tolerogenic cell therapy for application in organ transplantation.通过供者骨髓移植实现混合嵌合体：一种用于器官移植的耐受原性细胞治疗方法。
Curr Opin Organ Transplant. 2012 Feb;17(1):63-70. doi: 10.1097/MOT.0b013e32834ee68b.
10
Effect of Ex Vivo-Expanded Recipient Regulatory T Cells on Hematopoietic Chimerism and Kidney Allograft Tolerance Across MHC Barriers in Cynomolgus Macaques.体外扩增的受体调节性T细胞对食蟹猴MHC屏障间造血嵌合及肾移植耐受的影响
Transplantation. 2017 Feb;101(2):274-283. doi: 10.1097/TP.0000000000001559.
引用本文的文献
1
Antigen Specific Regulatory T Cells in Kidney Transplantation and Other Tolerance Settings.抗原特异性调节性 T 细胞在肾移植和其他耐受环境中的作用。
Front Immunol. 2021 Aug 26;12:717594. doi: 10.3389/fimmu.2021.717594. eCollection 2021.
2
Selective expansion of regulatory T cells using an orthogonal IL-2/IL-2 receptor system facilitates transplantation tolerance.使用正交白细胞介素-2/白细胞介素-2受体系统选择性扩增调节性T细胞有助于移植耐受。
J Clin Invest. 2021 Apr 15;131(8). doi: 10.1172/JCI139991.
3
Human pluripotent stem cell-derived insulin-producing cells: A regenerative medicine perspective.人多能干细胞衍生的胰岛素分泌细胞：再生医学视角。
Cell Metab. 2021 Apr 6;33(4):721-731. doi: 10.1016/j.cmet.2021.03.021.
4
Tregs and Mixed Chimerism as Approaches for Tolerance Induction in Islet Transplantation.调节性T细胞与混合嵌合体作为胰岛移植诱导免疫耐受的方法
Front Immunol. 2021 Jan 29;11:612737. doi: 10.3389/fimmu.2020.612737. eCollection 2020.
5
A Prospective Controlled Trial to Evaluate Safety and Efficacy of Expanded Recipient Regulatory T Cell Therapy and Tocilizumab Together With Donor Bone Marrow Infusion in HLA-Mismatched Living Donor Kidney Transplant Recipients (Trex001).一项前瞻性对照试验，评估在HLA配型不合的活体供肾移植受者中，扩增的受者调节性T细胞疗法与托珠单抗联合供体骨髓输注的安全性和有效性（Trex001）。
Front Med (Lausanne). 2021 Jan 27;7:634260. doi: 10.3389/fmed.2020.634260. eCollection 2020.
6
Myeloid-derived suppressor cells therapy enhance immunoregulatory properties in acute graft versus host disease with combination of regulatory T cells.髓源性抑制细胞疗法联合调节性T细胞可增强急性移植物抗宿主病中的免疫调节特性。
J Transl Med. 2020 Dec 14;18(1):483. doi: 10.1186/s12967-020-02657-6.
7
Enabling allogeneic therapies: CIRM-funded strategies for immune tolerance and immune evasion.实现异体疗法：CIRM 资助的免疫耐受和免疫逃逸策略。
Stem Cells Transl Med. 2020 Sep;9(9):959-964. doi: 10.1002/sctm.20-0079. Epub 2020 Jun 25.
8
Regulatory T cells in solid organ transplantation.实体器官移植中的调节性T细胞
Clin Transl Immunology. 2020 Feb 23;9(2):e01099. doi: 10.1002/cti2.1099. eCollection 2020.
本文引用的文献
1
Strategies for long-term preservation of kidney graft function.肾脏移植物功能的长期保护策略。
Lancet. 2017 May 27;389(10084):2152-2162. doi: 10.1016/S0140-6736(17)31283-7.
2
Chimerism-based tolerance in organ transplantation: preclinical and clinical studies.基于嵌合体的器官移植耐受性：临床前和临床研究
Clin Exp Immunol. 2017 Aug;189(2):190-196. doi: 10.1111/cei.12969. Epub 2017 Apr 20.
3
Origin of Enriched Regulatory T Cells in Patients Receiving Combined Kidney-Bone Marrow Transplantation to Induce Transplantation Tolerance.接受肾-骨髓联合移植以诱导移植耐受的患者中富集调节性T细胞的起源
Am J Transplant. 2017 Aug;17(8):2020-2032. doi: 10.1111/ajt.14251. Epub 2017 Apr 10.
4
Minor Antigen Disparities Impede Induction of Long Lasting Chimerism and Tolerance through Bone Marrow Transplantation with Costimulation Blockade.次要抗原差异通过骨髓移植联合共刺激阻断阻碍嵌合体和耐受的长期诱导。
J Immunol Res. 2016;2016:8635721. doi: 10.1155/2016/8635721. Epub 2016 Oct 31.
5
Effect of Ex Vivo-Expanded Recipient Regulatory T Cells on Hematopoietic Chimerism and Kidney Allograft Tolerance Across MHC Barriers in Cynomolgus Macaques.体外扩增的受体调节性T细胞对食蟹猴MHC屏障间造血嵌合及肾移植耐受的影响
Transplantation. 2017 Feb;101(2):274-283. doi: 10.1097/TP.0000000000001559.
6
Incomplete clonal deletion as prerequisite for tissue-specific minor antigen tolerization.不完全克隆删除作为组织特异性次要抗原耐受的前提。
JCI Insight. 2016 May 19;1(7):e85911. doi: 10.1172/jci.insight.85911.
7
Kidney Transplantation With Corticosteroids Alone After Haploidentical HSCT From The Same Donor.同供者单倍体造血干细胞移植后单独应用皮质类固醇的肾移植。
Transplantation. 2016 Oct;100(10):2219-21. doi: 10.1097/TP.0000000000001213.
8
Normalizing the environment recapitulates adult human immune traits in laboratory mice.使环境正常化可在实验室小鼠中重现成年人类的免疫特征。
Nature. 2016 Apr 28;532(7600):512-6. doi: 10.1038/nature17655. Epub 2016 Apr 20.
9
TGF-β-Induced Regulatory T Cells Directly Suppress B Cell Responses through a Noncytotoxic Mechanism.转化生长因子-β诱导的调节性T细胞通过非细胞毒性机制直接抑制B细胞反应。
J Immunol. 2016 May 1;196(9):3631-41. doi: 10.4049/jimmunol.1501740. Epub 2016 Mar 21.
10
Distinctive Expression of Bcl-2 Factors in Regulatory T Cells Determines a Pharmacological Target to Induce Immunological Tolerance.调节性T细胞中Bcl-2因子的独特表达决定了诱导免疫耐受的药理学靶点。
Front Immunol. 2016 Mar 1;7:73. doi: 10.3389/fimmu.2016.00073. eCollection 2016.
Zotero 插件