Yi Huanfa, Zhang Lianjun, Zhen Yu, He Xiaoyan, Zhao Yong
Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Cytokine. 2007 Jan;37(1):35-43. doi: 10.1016/j.cyto.2007.02.012. Epub 2007 Mar 26.
Dendritic cells (DCs), as an important part of antigen-presenting cells, can efficiently prime naïve T cell to induce or regulate immune responses. GM-CSF, combined with other growth factors, was used to induce the differentiation of immature or mature DCs from progenitors. Here, we investigated the effect of IL-5, a Th2 cytokine, on the differentiation and function of mouse DCs induced by GM-CSF in vitro. IL-5 significantly inhibited the differentiation of DCs induced by GM-CSF, but no effects on GM-CSF/IL-4 (GM/4) induced DCs. Compared with the conventional mouse DCs developed in the presence of GM-CSF and IL-4, mouse DCs induced by GM-CSF and IL-5 (refereed as to GM/5 DCs) possessed similar cellular morphology, but they expressed high level of CD11c, but low level of MHC II molecules, CD40 and CD86, which is consistent with the immature DC phenotype. In addition, GM/5 DCs showed significantly lower immunogenicity as indicated by their poor stimulating ability to allogeneic T cells in vitro, decreased expression of pro-inflammatory IL-6 and TNF-alpha, as well as increased expression of TGF-beta, compared with GM/4 DCs. Together, these data suggest that IL-5 could partially inhibit GM-CSF-induced DC differentiation which could be reversed by IL-4 in vitro.
树突状细胞(DCs)作为抗原呈递细胞的重要组成部分,能够有效地激活初始T细胞以诱导或调节免疫反应。GM-CSF与其他生长因子联合使用,可诱导祖细胞分化为未成熟或成熟的DCs。在此,我们研究了Th2细胞因子IL-5对体外GM-CSF诱导的小鼠DCs分化和功能的影响。IL-5显著抑制GM-CSF诱导的DCs分化,但对GM-CSF/IL-4(GM/4)诱导的DCs无影响。与在GM-CSF和IL-4存在下培养的传统小鼠DCs相比,GM-CSF和IL-5诱导的小鼠DCs(称为GM/5 DCs)具有相似的细胞形态,但它们表达高水平的CD11c,而MHC II分子、CD40和CD86的表达水平较低,这与未成熟DC表型一致。此外,与GM/4 DCs相比,GM/5 DCs在体外对同种异体T细胞的刺激能力较差,促炎细胞因子IL-6和TNF-α的表达降低,以及TGF-β的表达增加,表明其免疫原性显著降低。总之,这些数据表明IL-5可部分抑制GM-CSF诱导的DC分化,而IL-4在体外可逆转这种抑制作用。