Generation of antigen-specific, interleukin-10-producing T-cells using dendritic cell stimulation and steroid hormone conditioning
Generation of antigen-specific, interleukin-10-producing T-cells using dendritic cell stimulation and steroid hormone conditioning
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DOI：
10.1016/s0966-3274(03)00049-2
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发表时间：
2003-07-01
影响因子：
1.5
通讯作者：
Griffin, MD
中科院分区：
文献类型：
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作者：
Dong, XY;Bachman, LA;Griffin, MD
调控t细胞群在体内产生的机制尚不清楚。尽管如此，最近的一些研究提出了利用药物或修饰的抗原提呈细胞在体外产生具有调节能力的t细胞的可能性。在这项研究中，研究了糖皮质激素和1,25二羟基维生素D-3 (1,25（OH)(2)D-3）激动剂联合使用对树突状细胞（DC）刺激的抗原特异性CD4(+ve) t细胞的影响。在地塞米松和1,25(OH)(2) d -3类似物的存在下，经过多轮dc介导的刺激后，产生的t细胞具有以下特征：(a)在随后的抗原暴露后IL-10分泌增强，(b) IL-2和干扰素γ分泌减弱，(c)缺乏Th2 （il -4分泌）表型的诱导，(d)对原代t细胞增殖的显著抗原特异性抑制，以及(e)在体内保留对抗原存活和增殖的能力。这些分泌il -10的t细胞被称为“类固醇激素条件t细胞”。当将缺乏共刺激的dc群体用于体外类固醇激素条件刺激时，观察到两个额外的效应：(a)进一步倾向于抗原特异性IL-10的产生；(b)增强激活诱导的抑制受体CTLA-4 （CD152）的上调。结果表明，糖皮质激素和1,25(OH)(2)D-3激动剂可以调节dc介导的抗原特异性t细胞的体外生成，促进il -10的分泌，调节t细胞群。这种t细胞表型可以通过使用共刺激缺陷dc进一步增强。(C) 2003 Elsevier b.v.版权所有
The mechanisms by which regulatory T-cell populations are generated in vivo are poorly understood. Nonetheless, the possibility of generating T-cells with regulatory capacity ex vivo using pharmacologic agents or modified antigen presenting cells has been raised by a number of recent studies. In this study, the effect of combined glucocorticoid and 1,25 dihydroxyvitamin D-3 (1,25(OH)(2)D-3) agonists on dendritic cell (DC)-stimulated, antigen-specific CD4(+ve) T-cells was investigated. Following multiple rounds of DC-mediated stimulation in the presence of dexamethasone and an analog of 1,25(OH)(2)D-3, the resulting T-cells were characterized by: (a) enhanced IL-10 secretion upon subsequent antigen exposure, (b) attenuated secretion of IL-2 and interferon gamma, (c) lack of induction of Th2 (IL-4-secreting) phenotype, (d) significant antigen-specific suppression of primary T-cell proliferation and (e) retention of the ability to survive and proliferate to antigen in vivo. These IL-10-secreting T-cells were termed 'steroid hormone-conditioned T-cells'. When a co-stimulation-deficient population of DCs was employed for the in vitro, steroid hormone-conditioned stimulations, two additional effects were observed: (a) a further skewing towards antigen-specific IL-10 production and (b) enhanced activation-induced up-regulation of the inhibitory receptor CTLA-4 (CD152). It was concluded that DC-mediated generation of antigen-specific T-cells in vitro can be modulated to promote an IL-10-secreting, regulatory T-cell population using glucocorticoid and 1,25(OH)(2)D-3 agonists. This T-cell phenotype can be further enhanced by the use of costimulation-deficient DCs. (C) 2003 Elsevier B.V All rights reserved.