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贝拉西普与移植中的调节性T细胞：免疫耐受和移植物存活的协同策略

Belatacept and regulatory T cells in transplantation: synergistic strategies for immune tolerance and graft survival.

作者信息

Kim Gil-Ran, Nam Kyung-Ho, Choi Je-Min

机构信息

Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, Korea.

Research Institute for Natural Sciences, Hanyang University, Seoul, Korea.

出版信息

Clin Transplant Res. 2024 Dec 31;38(4):326-340. doi: 10.4285/ctr.24.0057. Epub 2024 Dec 18.

DOI:10.4285/ctr.24.0057
PMID:39690903
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11732762/
Abstract

Calcineurin inhibitors (CNIs) have been a cornerstone in solid organ transplantation for many years; however, their prolonged use is linked to significant adverse effects, most notably nephrotoxicity. Belatacept, a modified version of cytotoxic T lymphocyte antigen-4 immunoglobulin with increased binding affinity for its ligand, has emerged as a viable alternative to traditional CNIs due to its lower toxicity profile. Despite these benefits, belatacept is associated with a higher rate of acute rejection, which presents a challenge for long-term graft survival. This review reevaluates the limitations of belatacept in achieving long-term acceptance of transplants and highlights the importance of regulatory T (Treg) cells in maintaining immune tolerance and preventing graft rejection. Additionally, it discusses the potential benefits of combining therapies that boost Treg cells with belatacept to increase the effectiveness of immunosuppression and improve graft outcomes.

摘要

多年来，钙调神经磷酸酶抑制剂（CNIs）一直是实体器官移植的基石；然而，长期使用它们会带来显著的不良反应，最明显的是肾毒性。贝拉西普是细胞毒性T淋巴细胞抗原4免疫球蛋白的改良版本，对其配体的结合亲和力增加，由于其较低的毒性特征，已成为传统CNIs的一种可行替代方案。尽管有这些益处，但贝拉西普与较高的急性排斥反应发生率相关，这对移植物的长期存活构成了挑战。本综述重新评估了贝拉西普在实现移植长期接受方面的局限性，并强调了调节性T（Treg）细胞在维持免疫耐受和预防移植物排斥中的重要性。此外，还讨论了将增强Treg细胞的联合疗法与贝拉西普相结合以提高免疫抑制效果和改善移植物结局的潜在益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eef/11732762/9e15fe04c3bd/ctr-38-4-326-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eef/11732762/c226cd01140c/ctr-38-4-326-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eef/11732762/a289d0915a76/ctr-38-4-326-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eef/11732762/9e15fe04c3bd/ctr-38-4-326-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eef/11732762/c226cd01140c/ctr-38-4-326-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eef/11732762/a289d0915a76/ctr-38-4-326-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eef/11732762/9e15fe04c3bd/ctr-38-4-326-f3.jpg

相似文献

1
Belatacept and regulatory T cells in transplantation: synergistic strategies for immune tolerance and graft survival.贝拉西普与移植中的调节性T细胞：免疫耐受和移植物存活的协同策略
Clin Transplant Res. 2024 Dec 31;38(4):326-340. doi: 10.4285/ctr.24.0057. Epub 2024 Dec 18.
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Belatacept As an Alternative to Calcineurin Inhibitors in Patients with Solid Organ Transplants.贝拉西普在实体器官移植患者中作为钙调神经磷酸酶抑制剂的替代药物。
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本文引用的文献

1
The effect of abatacept on T-cell activation is not long-lived .阿巴西普对T细胞活化的作用并非持久。
Discov Immunol. 2024 Jan 4;3(1):kyad029. doi: 10.1093/discim/kyad029. eCollection 2024.
2
A humanized IL-2 mutein expands Tregs and prolongs transplant survival in preclinical models.一种人源化的 IL-2 突变体可扩增 Tregs 并延长临床前模型中的移植存活时间。
J Clin Invest. 2024 Mar 1;134(5):e173107. doi: 10.1172/JCI173107.
3
First-in-human therapy with Treg produced from thymic tissue (thyTreg) in a heart transplant infant.首例来源于胸腺组织（thyTreg）的 Treg 细胞治疗在心脏移植婴儿中的应用。
J Exp Med. 2023 Dec 4;220(12). doi: 10.1084/jem.20231045. Epub 2023 Oct 31.
4
Alleviating psoriatic skin inflammation through augmentation of Treg cells via CTLA-4 signaling peptide.通过 CTLA-4 信号肽增强 Treg 细胞来缓解银屑病皮肤炎症。
Front Immunol. 2023 Sep 25;14:1233514. doi: 10.3389/fimmu.2023.1233514. eCollection 2023.
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Targeted modulation of immune cells and tissues using engineered biomaterials.使用工程生物材料对免疫细胞和组织进行靶向调控。
Nat Rev Bioeng. 2023 Feb;1(2):107-124. doi: 10.1038/s44222-022-00016-2. Epub 2023 Jan 30.
6
Low Performance of Sinovac Vaccine Particularly With Belatacept Therapy in a Study With Different Types of COVID-19 Vaccines in Transplanted Patients.在一项针对移植患者的不同类型 COVID-19 疫苗的研究中，与贝拉西普治疗相比，科兴疫苗表现不佳。
Transplant Proc. 2023 Apr;55(3):500-507. doi: 10.1016/j.transproceed.2023.02.034. Epub 2023 Mar 1.
7
Activation of immune signals during organ transplantation.器官移植过程中的免疫信号激活。
Signal Transduct Target Ther. 2023 Mar 11;8(1):110. doi: 10.1038/s41392-023-01377-9.
8
Principles of regulatory T cell function.调节性 T 细胞功能的原则。
Immunity. 2023 Feb 14;56(2):240-255. doi: 10.1016/j.immuni.2023.01.004.
9
Low-dose interleukin-2 promotes immune regulation in face transplantation: A pilot study.低剂量白细胞介素 2 促进面部移植中的免疫调节：一项初步研究。
Am J Transplant. 2023 Apr;23(4):549-558. doi: 10.1016/j.ajt.2023.01.016. Epub 2023 Feb 4.
10
Early calcineurin-inhibitor to belatacept conversion in steroid-free kidney transplant recipients.在无类固醇的肾移植受者中早期将钙调磷酸酶抑制剂转换为贝利尤单抗。
Front Immunol. 2022 Dec 19;13:1096881. doi: 10.3389/fimmu.2022.1096881. eCollection 2022.