Cord blood CD4+CD25+-derived T regulatory cell lines express FoxP3 protein and manifest potent suppressor function
Cord blood CD4+CD25+-derived T regulatory cell lines express FoxP3 protein and manifest potent suppressor function
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DOI：
10.1182/blood-2004-06-2467
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发表时间：
2005-01-15
期刊：
影响因子：
20.3
通讯作者：
Porter, SB
中科院分区：
文献类型：
--
作者：
Godfrey, WR;Spoden, DJ;Porter, SB
CD 4（+）CD 25（+）调节性T细胞（T-reg）已被证明对小鼠自身和同种异体移植耐受性具有重要的调节作用。人T-reg细胞的研究受到外周血中存在的低数量和难以纯化的阻碍。我们发现，脐带血是一个优越的上级来源的T-reg-细胞分离和细胞系生成相比，成人血液。脐带血CD 4（+）CD 25（+）细胞易于纯化，并产生持续表现出有效抑制活性的细胞系，对同种异体混合淋巴细胞反应（MLR）的抑制率超过95%（30名供体中有29名）。培养的T-reg细胞阻断了MLR中的细胞因子积累，对趋化因子产生的抑制作用不太强。这些细胞系均匀地表达CD 25、CD 62 L、CCR 7、CD 27和细胞内细胞毒性T淋巴细胞抗原-4（CTLA 4）。FoxP 3蛋白特异性表达，而mRNA无特异性表达。在用抗CD 3/CD 28珠再刺激后，培养的T-reg细胞产生最少的细胞因子（白细胞介素-2 [IL-2]、干扰素-γ [IFN-γ]和IL-10），并优先表达肿瘤生长因子-β（TGF-β）潜伏相关蛋白。然而，细胞因子的生产，恢复到正常水平的佛波醇肉豆蔻酸酯乙酸酯（PMA）/离子霉素的再刺激。脐带血来源的培养抑制细胞功能主要独立于IL-10和TGF-β。这些结果表明，脐带血含有大量的T-reg前体细胞，在培养物活化后能够发挥有效的抑制功能。库存脐带血标本可作为免疫治疗的Treg细胞的现成来源。(C)2005年，美国血液学会。
CD4(+)CD25(+) T regulatory (T-reg) cells have been shown to critically regulate self and allograft tolerance in mice. Studies of human T-reg cells have been hindered by low numbers present in peripheral blood and difficult purification. We found that cord blood was a superior source for T-reg-cell isolation and cell line generation compared with adult blood. Cord blood CD4(+)CD25(+) cells were readily purified and generated cell lines that consistently exhibited potent suppressor activity, with more than 95% suppression of allogeneic mixed lymphocyte reactions (MLRs) (29 of 30 donors). Cultured T-reg cells blocked cytokine accumulation in MLRs, with a less robust inhibition of chemokine production. These cell lines uniformly expressed CD25, CD62L, CCR7, CD27, and intracellular cytotoxic T-lymphocyte antigen-4 (CTLA4). FoxP3 protein, but not mRNA, was specifically expressed. Upon restimulation with anti-CD3/CD28 beads, the cultured T-reg cells produced minimal cytokines (interleukin-2 [IL-2], interferon-gamma [IFN-gamma], and IL-10) and preferentially expressed tumor growth factor-beta (TGF-beta) latency associated protein. Cytokine production, however, was restored to normal levels by restimulation with phorbol myristate acetate (PMA)/ionomycin. Cord blood-derived cultured suppressor cell function was predominantly independent of IL-10 and TGF-beta. These results demonstrate cord blood contains a significant number of T-reg precursor cells capable of potent suppressor function after culture activation. Banked cord blood specimens may serve as a readily available source of Treg cells for immunotherapy. (C) 2005 by The American Society of Hematology.