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间充质基质细胞在实体器官移植中控制供体特异性记忆T细胞。

Mesenchymal stromal cells to control donor-specific memory T cells in solid organ transplantation.

作者信息

Cortinovis Monica, Casiraghi Federica, Remuzzi Giuseppe, Perico Norberto

机构信息

Clinical Research Center for Rare Diseases 'Aldo & Cele Daccò', IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Bergamo, Italy.

出版信息

Curr Opin Organ Transplant. 2015 Feb;20(1):79-85. doi: 10.1097/MOT.0000000000000145.

Abstract

PURPOSE OF REVIEW

Mesenchymal stromal cells (MSCs) represent a promising cell therapy to promote transplant tolerance, as they influence many cells involved in immune response. Herein, we review recent evidence on the ability of MSCs to inhibit antigen-induced memory T cell response in vitro and in preclinical studies as well as immunological studies in kidney transplant recipients highlighting the effects of MSC therapy on memory CD8 T-cell proliferation and function.

RECENT FINDINGS

MSCs are able to inhibit in-vitro proliferation and effector functions of memory T cells in response to auto-antigen and allo-antigen stimulation. MSC infusion in animal transplant models resulted in a skew of the balance between regulatory T cells and effector/memory T cells towards a pro-tolerogenic profile. MSC in clinical transplantation is in its infancy and limited numbers of clinical studies have performed immunomonitoring of MSC-treated patients. However, available data support the capability of MSCs to control effector/memory CD8 T-cell proliferation and donor-specific CD8 T-cell function long lasting in kidney transplant setting.

SUMMARY

Recent studies of MSCs in kidney transplantation highlight the anticipated add-on value of the immunomodulatory properties of bone marrow derived MSCs in persistently inhibiting donor-specific effector/memory CD8 T cells, an effect not shared by the current immunosuppressive drugs.

摘要

综述目的

间充质基质细胞(MSCs)作为一种有前景的细胞疗法,可促进移植耐受,因为它们能影响许多参与免疫反应的细胞。在此,我们综述了MSCs在体外和临床前研究中抑制抗原诱导的记忆T细胞反应的最新证据,以及肾移植受者的免疫学研究,重点介绍了MSC疗法对记忆性CD8 T细胞增殖和功能的影响。

最新发现

MSCs能够抑制记忆T细胞在自身抗原和同种异体抗原刺激下的体外增殖和效应功能。在动物移植模型中输注MSCs导致调节性T细胞与效应/记忆T细胞之间的平衡向促耐受状态倾斜。临床移植中的MSC尚处于起步阶段,仅有少数临床研究对接受MSC治疗的患者进行了免疫监测。然而,现有数据支持MSCs在肾移植环境中能够长期控制效应/记忆性CD8 T细胞增殖和供体特异性CD8 T细胞功能。

总结

最近关于MSCs在肾移植中的研究突出了骨髓来源的MSCs免疫调节特性在持续抑制供体特异性效应/记忆性CD8 T细胞方面的预期附加价值,这一作用是目前免疫抑制药物所不具备的。

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