Human regulatory T cells of G-CSF mobilized allogeneic stem cell donors qualify for clinical application.
Human regulatory T cells of G-CSF mobilized allogeneic stem cell donors qualify for clinical application.
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DOI：
10.1371/journal.pone.0051644
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Franzke A
中科院分区：
文献类型：
--
作者：
Ukena SN;Velaga S;Goudeva L;Ivanyi P;Olek S;Falk CS;Ganser A;Franzke A
最近的临床研究表明，调节性T细胞（Tregs）在控制造血干细胞移植（SCT）中的移植物抗宿主病方面具有很高的效力。然而，treg的过继性转移受到其在未刺激供体中的低频率的限制，并且人们相当担心G-CSF诱导的SC动员可能对treg的稳定性和功能产生负面影响。从G-CSF动员的SC移植物中分离treg将把这种新的耐受诱导策略扩展到不相关的环境，并简化全球临床应用。我们对SC供者在G-CSF动员前后的CD4+CD25highCD127−Tregs的表型、功能和稳定性进行了表征。G-CSF作用后Treg细胞产量显著增加。供体Tregs在SC动员后保持其细胞因子谱、表型特征和体外扩增能力。最重要的是，体内G-CSF刺激的Tregs在体外扩增后仍然高度抑制效应T细胞的增殖，并在表观遗传学研究中表现出稳定的表型。CXCR3的表面表达瞬间降低。然而，供体来源的treg在G-CSF刺激后保持其迁移特性。因此，从G-CSF动员的SC供体中过继移植treg似乎是一种可行且安全的策略，可用于异体SCT的临床应用。
Recent clinical studies demonstrate the high potency of regulatory T cells (Tregs) to control graft-versus-host disease in hematopoietic stem cell transplantation (SCT). However, the adoptive transfer of Tregs is limited by their low frequency in unstimulated donors and considerable concerns that G-CSF induced SC mobilization might have negative effects on the stability and function of Tregs. The isolation of Tregs from the G-CSF mobilized SC grafts would extend this novel strategy for tolerance induction to the unrelated setting and simplify global clinical application. We characterized CD4+CD25highCD127− Tregs from SC donors before and after G-CSF mobilization for their phenotype, function, and stability. After G-CSF application the Treg cell yield increased significantly. Donor Tregs retained their cytokine profile, phenotypic characteristics and in vitro expansion capacity after SC mobilization. Most importantly, in vivo G-CSF stimulated Tregs remained highly suppressive on the proliferation of effector T cells, also after in vitro expansion, and displayed a stable phenotype in epigenetic studies. The surface expression of CXCR3 is transiently reduced. However, donor-derived Tregs maintain their migratory properties after G-CSF stimulation. Therefore, the adoptive transfer of Tregs from G-CSF mobilized SC donors seems to be a feasible and safe strategy for clinical application in allogeneic SCT.
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影响因子：
15.3
作者：
Kimmig, Sonja;Przybylski, Grzegorz K;Schmidt, Christian A;Laurisch, Katja;Mowes, Beate;Radbruch, Andreas;Thiel, Andreas
通讯作者：
Thiel, Andreas
影响因子：
20.3
作者：
Kean, Leslie S.;Sen, Sharon;Donahue, Robert E.
通讯作者：
Donahue, Robert E.
影响因子：
20.3
作者：
Franzke, A;Piao, WJ;Ganser, A
通讯作者：
Ganser, A
影响因子：
32.4
作者：
Semerad, CL;Liu, FL;Link, DC
通讯作者：
Link, DC
影响因子：
20.3
作者：
Boneberg, EM;Hareng, L;Hartung, T
通讯作者：
Hartung, T