Ex vivo expanded human CD4+CD25+Foxp3+regulatory T cells prevent lethal xenogenic graft versus host disease (GVHD)
Ex vivo expanded human CD4+CD25+Foxp3+regulatory T cells prevent lethal xenogenic graft versus host disease (GVHD)
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DOI：
10.1016/j.cellimm.2009.03.013
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发表时间：
2009-01-01
影响因子：
4.3
通讯作者：
Li, Li
中科院分区：
文献类型：
--
作者：
Cao, Tinghua;Soto, Allis;Li, Li
小鼠研究表明，输注CD4+CD25+调节性T细胞(Tregs)可以预防骨髓移植(BMT)后移植物抗宿主病(GVHD)的死亡。但人类Tregs对GVHD的潜在影响尚未得到很好的证明。在这项研究中，我们证明了从健康供者的外周血中提取的人Tregs可以在2-3周内体外扩增到临床相关的细胞数量，同时保持Foxp3、CID25、CTLA-4和CD62L的表达以及体外抑制功能。此外，在NOD/SCID小鼠体内注射人PBL可诱导致死性异种GVHD，但将扩增的人Tregs与人PBL共转移可显著提高NOD/SCID小鼠的存活率，减轻GVHD症状，并抑制人免疫球蛋白G/IgM的产生。这些结果表明，体外扩增的人Tregs保留了体内的抑制活性，并预防了致死性的异种GVHD，揭示了扩增的人Tregs治疗GVHD的潜力。(C)2009 Elsevier Inc.保留所有权利。
Mouse studies demonstrated that infusion of CD4+CD25+ regulatory T cells (Tregs) prevented graft versus host disease (GVHD) lethality after bone marrow transplantation (BMT). But the potential impact of human Tregs on GVHD has not been well demonstrated. In this study, we demonstrated that human Tregs enriched from peripheral blood of healthy donors could be expanded ex vivo to clinically relevant cell numbers in 2-3 weeks while maintaining Foxp3, CID25, CTLA-4, and CD62L expression as well as in vitro suppressive function. Furthermore, injection of human PBL into NOD/SCID mice induced lethal xenogenic GVHD, but co-transfer of expanded human Tregs with human PBL significantly enhanced survival, reduced GVHD symptoms, and inhibited human IgG/IgM production in the NOD/SCID mice. These results demonstrated that ex vivo expanded human Tregs retained their in vivo suppressive activity and prevented lethal xenogeneic GVHD, revealing the therapeutic potential of expanded human Tregs for GVHD. (C) 2009 Elsevier Inc. All rights reserved.