A minimal human immunostimulatory CpG motif that potently induces IFN-γ and IFN-α production
A minimal human immunostimulatory CpG motif that potently induces IFN-γ and IFN-α production
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DOI：
10.1002/eji.200323948
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发表时间：
2003-08-01
影响因子：
5.4
通讯作者：
Coffman, RL
中科院分区：
文献类型：
--
作者：
Fearon, K;Marshall, JD;Coffman, RL
最近的报道表明，含有CpG基序的免疫刺激序列（ISS）对哺乳动物细胞发挥免疫增强功能的长度要求最小（大于或等于12个碱基）。本研究表明，短的ISS（5-7个碱基）在吸附到阳离子poly（D,L-lactide-co-glycolide）微粒（cPLGA）表面时，可以诱导人外周血单核细胞分泌ifn - γ和ifn - α，而ISS本身没有活性。利用这一技术，我们发现了从人类细胞诱导ifn - γ和ifn - α的最小ISS序列：5‘-TCGXX-3’。这些较短的ISS/cPLGA配方针对PDC的方式与较长的ISS ODN类似，后者的活性不需要cPLGA（但可以通过cPLGA增强）。短ISS/cPLGA刺激的PDC会增加ISS的摄取和细胞因子的产生，包括ifn - α。然而，ISS反应的B细胞对短ISS/cPLGA没有反应，强调了该制剂的浆细胞样树突状细胞选择性。这些结果描述了一种新的技术，用于制定活性，但非常短，ISS寡脱氧核苷酸，允许解剖和表征最小的免疫刺激CpG基序。
Recent reports have shown that immunostimulatory sequences (ISS) containing CpG motifs have minimal length requirements (greater than or equal to12 bases) for the exertion of immune-enhancing function upon mammalian cells. Herein we demonstrate that short ISS (5-7 bases), which exhibit no activity on their own, induce IFN-gamma and IFN-alpha secretion from human peripheral blood mononuclear cells when adsorbed to the surface of cationic poly(D,L-lactide-co-glycolide) microparticles (cPLGA). Utilizing this technique, we discovered a minimal ISS sequence for induction of IFN-gamma and IFN-alpha from human cells: 5'-TCGXX-3'. These short ISS/cPLGA formulations targeted PDC in similar fashion to longer ISS ODN, the activity of which does not require (but is enhanced by) cPLGA. PDC stimulated with short ISS/cPLGA responded with enhanced uptake of ISS and elevated production of cytokines, including IFN-alpha. However, ISS-responsive B cells did not respond to short ISS/cPLGA, underlining the plasmacytoid dendritic cell selectivity of this formulation. These results describe a novel technique for formulating active, but very short, ISS oligodeoxynucleotide that allows for the dissection and characterization of minimal immunostimulatory CpG motifs.