IFN-γ Enhances TH1 Polarisation of Monocyte-derived Dendritic Cells Matured with Clinical-grade Cytokines Using Serum-free Conditions
IFN-γ Enhances TH1 Polarisation of Monocyte-derived Dendritic Cells Matured with Clinical-grade Cytokines Using Serum-free Conditions
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IFN-γ 增强在无血清条件下用临床级细胞因子成熟的单核细胞衍生树突细胞的 TH1 极化
DOI：
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
M. Azemar
中科院分区：
文献类型：
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作者：
B. Hildenbrand;D. Lorenzen;B. Sauer;Christian Hertkorn;M. Freudenberg;J. Peters;T. Nesselhut;C. Unger;M. Azemar
使用无血清条件，人单核细胞衍生的树突状细胞（MoDC）在批准和标准化的临床条件下倾向于在TH 1极化方向上不充分地成熟。然而，为了启动有效的肿瘤抗原特异性细胞毒性T细胞应答，诱导不同的T H1应答是有利的。因此，为了改善TH 1极化，在无血清培养基中用临床级细胞因子或脂多糖（LPS）研究了干扰素-γ（IFN- γ）对MoDC成熟的影响，重点是活力、表型特征、细胞因子谱和再刺激能力。如在先前的研究中，我们证实了在活力和表型特征方面，由肿瘤坏死因子-α（TNF- α）、白细胞介素（IL）-1 β、IL-6和前列腺素（PG）E2组成的细胞因子混合物最有效地成熟MoDC。然而，这些精氨酸成熟的MoDC分泌相对高水平的IL-10和仅低水平的IL-12 p70。值得注意的是，如果加入IFN- γ，可以检测到显著较低水平的IL-10伴随较高水平的IL-12 p70。IFN- γ预处理不能改善MoDCs的表型特征和TH 1极化。然而，用临床级细胞因子和IFN- γ成熟的MoDC可以用IFN- γ最有效地再刺激。总之，我们的工作表明，
Using serum-free conditions, human monocyte- derived dendritic cells (MoDCs) tend to mature insufficiently in a T H 1-polarizing direction under approved and standardized clinical conditions. However, for the initiation of an efficient tumour antigen-specific cytotoxic T-cell response, the induction of a distinct T H 1 response is favourable. Therefore, to improve T H 1 polari sation, the influence of interferon-gamma (IFN- γ) on the maturation of MoDCs was investigated with clinical-grade cytokines or lipopolysaccharide (LPS) in serum-free medium focusing on the viability, phenotypic characteristics, cytokine profile and restimulating capacities. As in previous research, we confirmed that in respect of viability and phenotypic characteristics, cytokine cocktails consisting of tumour necrosis factor-alpha (TNF- α), interleukin (IL)-1 β, IL-6 and prostaglandin (PG) E 2 , mature MoDCs most efficiently. However, these cytokine-matured MoDCs secreted relatively high levels of IL-10 and only low levels of IL-12p70. Remarkably, if IFN- γ was added, significantly lower levels of IL-10 concomitant with higher levels of IL-12p70 could be detected. Pretreatment with IFN- γ did not improve the phenotypic characteristics nor the T H 1 polarisation of MoDCs. Nevertheless, MoDCs matured with clinical-grade cytokines and IFN- γ could be re-stimulated most effectively with IFN- γ. In conclusion, our work demonstrates that
DOI：
10.1073/pnas.93.6.2588
发表时间：
1996-03-19
影响因子：
11.1
作者：
Zhou, LJ;Tedder, TF
通讯作者：
Tedder, TF