CpG DNA: A potent signal for growth, activation, and maturation of human dendritic cells
CpG DNA: A potent signal for growth, activation, and maturation of human dendritic cells
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DOI：
10.1073/pnas.96.16.9305
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发表时间：
1999-08-03
影响因子：
11.1
通讯作者：
Krieg, AM
中科院分区：
文献类型：
--
作者：
Hartmann, G;Weiner, GJ;Krieg, AM
在特定的碱基背景下，含有未甲基化CpG二核苷酸的DNA分子（“CpG基序”）在啮齿动物中是极好的佐剂，但它们对人类细胞的影响尚不清楚。树突状细胞（dc）在先天免疫系统和获得性免疫系统之间形成联系，并可能影响辅助性T细胞1 （Th1）和Th2免疫反应之间的平衡。我们评估了CpG寡核苷酸单独使用或与粒细胞-巨噬细胞集落刺激因子（GMCSF）联合使用对不同类型纯化的人树突状前体细胞的影响。对于从人血液中分离的原代树突状前体细胞，单独使用CpG寡核苷酸在促进树突状细胞的存活和成熟（CD83表达）以及Ii类MHC和共刺激分子CD40、CD54和CD86的表达方面优于GMCSF。cd4阳性和cd4阴性的外周血树突状前体细胞均对与GMCSF协同作用的CpG DNA有应答，但这些dc对脂多糖（LPS）的应答不明显。相比之下，单核细胞来源的dc对CpG没有反应，但它们对LPS高度敏感，这表明在不同的dc亚群中CpG和LPS敏感性之间存在负相关。与GMCSF相比，CpG处理的外周血dc在混合淋巴细胞反应中表现出更强的功能活性，并诱导T细胞分泌更多的Th1细胞因子。这些发现表明，特定CpG基序能够强烈激活人类dc的某些亚群，从而促进Th1样免疫反应，并支持基于CpG dna的试验用于癌症、过敏和传染病的免疫治疗。
DNA molecules containing unmethylated CpG-dinucleotides in particular base contexts ("CpG motifs") are excellent adjuvants in rodents, but their effects on human cells have been less clear. Dendritic cells (DCs) form the link between the innate and the acquired immune system and may influence the balance between T helper 1 (Th1) and Th2 immune responses. We evaluated the effects of CpG oligodeoxynucleotides alone or in combination with granulocyte-macrophage colony-stimulating factor (GMCSF) on different classes of purified human DCs, For primary dendritic precursor cells isolated from human blood, CpG oligonucleotides alone were superior to GMCSF in promoting survival and maturation (CD83 expression) as well as expression of class Ii MHC and the costimulatory molecules CD40, CD54, and CD86 of DCs, Both CD4-positive and CD4-negative peripheral blood dendritic precursor cells responded to CpG DNA which synergized with GMCSF but these DCs showed little response to lipopolysaccharide (LPS). In contrast, monocyte-derived DCs did not respond to CpG, but they were highly sensitive to LPS, suggesting an inverse correlation between CpG and LPS sensitivity in different subsets of DCs. Compared with GMCSF, CpG-treated peripheral blood DCs showed enhanced functional activity in the mixed lymphocyte reaction and induced T cells to secrete increased levers of Th1 cytokines, These findings demonstrate the ability of specific CpG motifs to strongly activate certain subsets of human DCs to promote Th1-like immune responses, and support the use of CpG DNA-based trials for immunotherapy against cancer, allergy, and infectious diseases.