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CD4+CD25+ 调节性 T 细胞衍生的外泌体延长大鼠肾移植模型的移植物存活时间。

CD4+CD25+ regulatory T cells-derived exosomes prolonged kidney allograft survival in a rat model.

机构信息

Department of Nephrology, 422 Hospital of PLA, Zhanjiang, Jiangshu 52400, China; Department of Urology, Xinqiao Hospital, Third Military Medical University, ChongQing 400037, China.

出版信息

Cell Immunol. 2013 Sep-Oct;285(1-2):62-8. doi: 10.1016/j.cellimm.2013.06.010. Epub 2013 Jun 28.

DOI:10.1016/j.cellimm.2013.06.010
PMID:24095986
Abstract

CD4(+)CD25(+) regulatory T cells (Tregs) are negative regulators of the immune system that induce and maintain immune tolerance. Exosomes are natural products released from many sources and play a role in antigen presentation, immunoregulation, and signal transduction. In order to determine whether exosomes can be released from Tregs and participate in transplantation tolerance, we isolated and purified Tregs-derived exosomes and established a rat model of kidney transplantation. We then transferred the autologous exosomes into recipients to observe the effect of transplantation tolerance in vivo and in vitro. From in vivo study, serum analysis and histology showed that the function of exosomes can postpone allograft rejection and prolong the survival time of transplanted kidney. From in vitro study, exosomes possessed the capacity to suppress T cells proliferation. Taken together, these results suggest that the Tregs-derived exosomes have a suppressive role on acute rejection and inhibit T cells proliferation, especially exosomes derived from donor-type Tregs, which imply that the Tregs-derived exosomes are one of far-end regulation mechanisms of Tregs. Thus, exosomes released from Tregs could be considered as a possible immunosuppressive reagent for the treatment of transplant rejection.

摘要

CD4(+)CD25(+) 调节性 T 细胞(Tregs)是免疫系统的负调节剂,可诱导和维持免疫耐受。外泌体是多种来源释放的天然产物,在抗原呈递、免疫调节和信号转导中发挥作用。为了确定 Tregs 是否可以释放外泌体并参与移植耐受,我们分离和纯化了 Tregs 衍生的外泌体,并建立了大鼠肾移植模型。然后,我们将自体外泌体转移到受者体内,以观察体内和体外移植耐受的效果。从体内研究来看,血清分析和组织学表明,外泌体的功能可以延缓同种异体移植物排斥反应,延长移植肾的存活时间。从体外研究来看,外泌体具有抑制 T 细胞增殖的能力。综上所述,这些结果表明 Tregs 衍生的外泌体对急性排斥反应具有抑制作用,并抑制 T 细胞增殖,特别是供体型 Tregs 衍生的外泌体,这意味着 Tregs 衍生的外泌体是 Tregs 的远位调节机制之一。因此,Tregs 释放的外泌体可以被认为是治疗移植排斥的一种潜在的免疫抑制试剂。

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