In vitro expanded human CD4+CD25+ regulatory T cells suppress effector T cell proliferation
In vitro expanded human CD4+CD25+ regulatory T cells suppress effector T cell proliferation
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DOI：
10.1016/j.clim.2005.02.017
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发表时间：
2005-04-01
影响因子：
8.6
通讯作者：
Bluestone, JA
中科院分区：
文献类型：
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作者：
Earle, KE;Tang, Q;Bluestone, JA
调节性T细胞（Regulatory T cells，Tcells）在自身免疫和免疫耐受的平衡中起着重要作用，与多种自身免疫性疾病有关。然而，外周血中的少量TbR限制了它们的治疗潜力。因此，我们开发了一种方案，该方案将允许扩增TdR，同时保留其抑制活性。我们从人外周血中分离出CD 4 + CD 25 hi细胞，并在存在抗CD 3和抗CD 28磁性Xcyte（TM）Dynabeads（R）和高浓度外源性白细胞介素（IL）-2的情况下进行体外扩增。T细胞被有效地扩增高达200倍，同时保持CD 25和T细胞的其他标志物（CD 62 L、HLA-DR、CCR 6和FOXP 3）的表面表达。在用抗-CD 3或同种异体抗原刺激的共培养物中，扩增的TcB抑制应答者PBMC的增殖和细胞因子分泌。Treg扩增是在考虑将TdR作为自身免疫性或移植物抗宿主病患者的治疗干预之前的关键第一步。(c)2005年爱思唯尔公司All rights reserved.
Regulatory T cells (Tregs) have been shown to be critical in the balance between autoimmunity and tolerance and have been implicated ill several human autoimmune diseases. However, the small number of Tregs in peripheral blood limits their therapeutic potential. Therefore, we developed a protocol that would allow for the expansion of Tregs while retaining their suppressive activity. We isolated CD4+CD25 hi cells from human peripheral blood and expanded them in vitro ill the presence of anti-CD3 and anti-CD28 magnetic Xcyte (TM) Dynabeads (R) and high concentrations of exogenous Interleukin (IL)-2. Tregs were effectively expanded up to 200-fold while maintaining surface expression of CD25 and other markers of Tregs: CD62L, HLA-DR, CCR6, and FOXP3. The expanded Tregs suppressed proliferation and cytokine secretion of responder PBMCs in co-cultures stimulated with anti-CD3 or alloantigen. Treg expansion is a critical first step before consideration of Tregs as a therapeutic intervention in patients with autoimmune or graft-versus-host disease. (c) 2005 Elsevier Inc. All rights reserved.