G-CSF as immune regulator in T cells expressing the G-CSF receptor:: implications for transplantation and autoimmune diseases
G-CSF as immune regulator in T cells expressing the G-CSF receptor:: implications for transplantation and autoimmune diseases
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DOI：
10.1182/blood-2002-04-1200
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发表时间：
2003-07-15
期刊：
影响因子：
20.3
通讯作者：
Ganser, A
中科院分区：
文献类型：
--
作者：
Franzke, A;Piao, WJ;Ganser, A
来自实验模型、体外研究和临床数据的结果表明，粒细胞集落刺激因子(G-CSF)刺激改变T细胞功能并诱导Th2免疫反应。在外周干细胞移植中，G-CSF对T细胞的免疫调节作用导致了意想不到的急性移植物抗宿主病的低发生率。然而，G-CSF治疗后T细胞反应性和/或同种异体反应性降低的潜在机制仍不清楚。与一般认为的G-CSF通过单核细胞和树突状细胞作用于T细胞不同，我们的研究结果清楚地表明，在体内和体外，G-CSF受体在单细胞水平上表达在II类和II类限制性T细胞中。动力学研究表明，在G-CSF暴露下，T细胞中G-CSF受体的诱导和功能活性。通过对经G-CSF处理的干细胞供者的T细胞的表达谱进行分析，可以确定几个免疫调节基因，这些基因受体内G-CSF给药的调节(例如，LFA1-α，ISGF3-伽马)，可能与反应性和/或同种异体反应性降低有关。最重要的是，体内用G-CSF治疗T细胞可诱导Th2免疫反应的主要转录因子GATA-3，同时伴随着自发分泌IL-4的增加。因此，G-CSF是一种强大的T细胞免疫调节剂，是治疗急性移植物抗宿主病以及与Th1/Th2失衡相关的疾病(如骨髓衰竭综合征和自身免疫性疾病)的一种有前景的治疗工具。(C)2003年，由美国血液病学会提供。
Results from experimental models, in vitro studies, and clinical data indicate that granulocyte colony-stimulating factor (G-CSF) stimulation alters T-cell function and induces Th2 immune responses. The immune modulatory effect of G-CSF on T cells results in an unexpected low incidence of acute graft-versus-host disease in peripheral stem cell transplantation. However, the underlying mechanism for the reduced reactivity and/or alloreactivity of T cells upon G-CSF treatment is still unknown. In contrast to the general belief that G-CSF acts exclusively on T cells via monocytes and dendritic cells, our re-suits clearly show the expression of the G-CSF receptor in class II- and II-restricted T cells at the single-cell level both in vivo and in vitro. Kinetic studies demonstrate the induction and functional activity of the G-CSF receptor in T cells upon G-CSF exposure. Expression profiling of T cells from G-CSF-treated stem cell donors allowed identification of several immune modulatory genes, which are regulated upon G-CSF administration in vivo (eg, LFA1-alpha, ISGF3-gamma) and that are likely responsible for the reduced reactivity and/or alloreactivity. Most importantly, the induction of GATA-3, the master transcription factor for a Th2 immune response, could be demonstrated in T cells upon G-CSF treatment in vivo accompanied by an increase of spontaneous interleukin-4 secretion. Hence, G-CSF is a strong immune regulator of T cells and a promising therapeutic tool in acute graft-versus-host disease as well as in conditions associated with Th1/Th2 imbalance, such as bone marrow failure syndromes and autoimmune diseases. (C) 2003 by The American Society of Hematology.