Potential Application of T-Follicular Regulatory Cell Therapy in Transplantation.
Potential Application of T-Follicular Regulatory Cell Therapy in Transplantation.
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滤泡调节性 T 细胞疗法在移植中的潜在应用。
DOI：
10.3389/fimmu.2020.612848
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发表时间：
2020
影响因子：
7.3
通讯作者：
Lombardi G
中科院分区：
文献类型：
--
作者：
Dudreuilh C;Basu S;Scottà C;Dorling A;Lombardi G
调节性T细胞（Tregs）构成了一小部分循环CD4+ T细胞，其功能是维持体内平衡和防止自身免疫。鉴于其强大的免疫抑制和促进耐受性的特性，Tregs已成为一个有趣的潜在候选者，用于治疗诸如实体器官移植或治疗自身免疫性和炎症性疾病。临床研究已经证明了多克隆扩增Tregs在移植物抗宿主病、1型糖尿病以及最近的肾和肝移植中的安全性。然而，treg是异质的。最近的研究表明，只有一小部分称为T滤泡调节细胞（Tfr）的treg调节生发中心内B细胞和T滤泡辅助细胞（Tfh）之间的相互作用。由于对人类次级淋巴器官取样的挑战，Tfr主要在小鼠模型中被描述。然而，新兴的人类研究将Tfr描述为CD4+CD25+FOXP3+CXCR5+细胞，根据其在血液或生发中心的定位，具有不同水平的PD-1和ICOS表达。它们在移植中的确切作用仍有待阐明。然而，鉴于这些细胞调节抗体对同种抗原反应的潜在能力，在需要调节B细胞反应的情况下，探索翻译应用具有很大的兴趣。在这里，我们回顾了目前对Tfr的认识及其在人类疾病和移植中的作用。我们还讨论了Tfr治疗在移植中的潜在应用，并研究了Tfr在抗体产生、急性和慢性排斥反应和三级淋巴器官中作用的证据。此外，还将探讨免疫抑制对Tfr的潜在影响。在临床前研究的基础上，我们将分析Tfr治疗在实体器官移植中的基本原理，并总结在Tfr治疗进入临床实践之前需要克服的不同挑战。
Regulatory T cells (Tregs) constitute a small proportion of circulating CD4+ T cells that function to maintain homeostasis and prevent autoimmunity. In light of their powerful immunosuppressive and tolerance-promoting properties, Tregs have become an interesting potential candidate for therapeutic use in conditions such as solid organ transplant or to treat autoimmune and inflammatory conditions. Clinical studies have demonstrated the safety of polyclonally expanded Tregs in graft-versus-host disease, type 1 diabetes, and more recently in renal and liver transplantation. However, Tregs are heterogenous. Recent insights indicate that only a small proportion of Tregs, called T follicular regulatory cells (Tfr) regulate interactions between B cells and T follicular helper (Tfh) cells within the germinal center. Tfr have been mainly described in mouse models due to the challenges of sampling secondary lymphoid organs in humans. However, emerging human studies, characterize Tfr as being CD4+CD25+FOXP3+CXCR5+ cells with different levels of PD-1 and ICOS expression depending on their localization, in the blood or the germinal center. The exact role they play in transplantation remains to be elucidated. However, given the potential ability of these cells to modulate antibody responses to allo-antigens, there is great interest in exploring translational applications in situations where B cell responses need to be regulated. Here, we review the current knowledge of Tfr and the role they play focusing on human diseases and transplantation. We also discuss the potential future applications of Tfr therapy in transplantation and examine the evidence for a role of Tfr in antibody production, acute and chronic rejection and tertiary lymphoid organs. Furthermore, the potential impact of immunosuppression on Tfr will be explored. Based on preclinical research, we will analyse the rationale of Tfr therapy in solid organ transplantation and summarize the different challenges to be overcome before Tfr therapy can be implemented into clinical practice.
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影响因子：
30.5
作者：
Clement, Rachel L.;Daccache, Joe;Sage, Peter T.
通讯作者：
Sage, Peter T.
影响因子：
8.2
作者：
Ekman, Ilse;Ihantola, Emmi-Leena;Kinnunen, Tuure
通讯作者：
Kinnunen, Tuure
DOI：
10.1038/nri3212
发表时间：
2012-05-11
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
16.6
作者：
Aloulou M;Carr EJ;Gador M;Bignon A;Liblau RS;Fazilleau N;Linterman MA
通讯作者：
Linterman MA
影响因子：
5.4
作者：
Brown, Kathryn;Sacks, Steven H.;Wong, Wilson
通讯作者：
Wong, Wilson