GM-CSF promotes differentiation of human dendritic cells and T lymphocytes toward a predominantly type 1 proinflammatory response
GM-CSF promotes differentiation of human dendritic cells and T lymphocytes toward a predominantly type 1 proinflammatory response
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DOI：
10.1016/j.exphem.2007.05.001
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发表时间：
2007-08-01
影响因子：
2.6
通讯作者：
Reddy, Vijay
中科院分区：
文献类型：
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作者：
Eksioglu, Erika A.;Mahmood, Syed S.;Reddy, Vijay
Objective.我们最近证实，具有高水平循环树突状细胞（DC）和白细胞介素（IL）-12的患者与造血干细胞移植后癌症复发率降低相关。确定一种可以促进这些免疫功能的生长因子可能具有有益的抗肿瘤作用。我们研究了粒细胞-巨噬细胞集落刺激因子（GM-CSF）诱导IL-12产生并使T淋巴细胞向促炎反应极化的假设。用GM-CSF培养外周血单核细胞（PBMC）、T淋巴细胞和抗原呈递细胞（APC），并与无生长因子（对照）、G-CSF或GM-CSF和G-CSF两者进行比较。用脂多糖或凝集素（植物血凝素）使细胞成熟。类型1和类型。采用酶联免疫吸附法测定2种细胞因子。混合淋巴细胞反应检测GM-CSF刺激的APC诱导的同种异体T淋巴细胞增殖。流式细胞仪检测DC。在用GM-CSF刺激PBMC、T淋巴细胞和APC后，I型（IL-12、干扰素-γ、肿瘤坏死因子-α）细胞因子水平增加，而2型（IL-10和IL-4）细胞因子水平降低。经GNI-CSF处理的APC可诱导同种异体T细胞的更高增殖。CD 11 c和CD 123阳性DC在GM-CSF作用下增殖。GM-CSF可使DC的DC 1和DC 2亚型表达增加。GM-CSF诱导人PBMC、T淋巴细胞和APC产生1型促炎细胞因子。2型细胞因子被GM-CSF下调，同种异体T细胞的增殖增加。这些结果证明了GM-CSF作为免疫刺激的临床试剂的潜力。(c)2007 ISEH -血液学和干细胞学会。爱思唯尔公司出版
Objective. We recently demonstrated that patients with high levels of circulating dendritic cells (DC) and interleukin (IL)-12 are associated with reduced cancer relapse after hematopoietic stem cell transplantation. Identifying a growth factor that can promote these immune functions may have beneficial anti-tumor effects. We investigated the hypothesis that granulocyte-macrophage colony-stimulating factor (GM-CSF) induces IL-12 production and polarizes T lymphocytes toward a proinflammatory response.Materials and Methods. Peripheral blood mononuclear cells (PBMC), T lymphocytes, and antigen-presenting cells (APC) were cultured with GM-CSF and compared with no growth factors (control), G-CSF, or both GM-CSF and G-CSF. Cells were matured with either lipopolysaccharide or lectin (phytohemagglutinin). Type 1 and type. 2 cytokines, were, measured by enzyme-linked immunosorbent assay. Induction of allogeneic T-lymphocyte proliferation induced by GM-CSF-stimulated APC was measured by mixed lymphocyte reaction. DC were measured by flow cytometry.Results. Levels of type I (IL-12, interferon-gamma, tumor necrosis factor-alpha) cytokines increased while type 2 (IL-10 and IL-4) cytokines decreased after stimulation of PBMC, T lymphocytes, and APC with GM-CSF. APC treated with GNI-CSF induced higher proliferation of allegeneic T cells. CD11c and CD123-positive DC proliferated after exposure to GM-CSF. Both subtypes of DC (DC1 and DC2) were increased by GM-CSF.Conclusions. GM-CSF induces production of type 1 proinflammatory cytokines by human PBMC, T lymphocytes, and APC. Type 2 cytokines are downregulated by GM-CSF and proliferation of allogeneic T cells is increased. These results demonstrate the potential for GM-CSF as a clinical agent for immune stimulation. (c) 2007 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.