Synthetic oligodeoxynucleotides inhibits IgE induction in human lymphocytes.

含有未甲基化CpG基序的合成寡脱氧核苷酸（ODNs）具有刺激小鼠Th-1应答的能力。已知Th-1细胞因子作为IgE产生的下调因子。在这项研究中，我们调查是否合成ODNs抑制IgE的生产从正常供体的人PBMC与白细胞介素-4（IL-4）和抗CD 40单克隆抗体（mAb）在体外刺激。从牛分枝杆菌BCG的MPB-70基因cDNA中随机选取30个单链寡核苷酸序列，发现CGTACG和AAGGTT两种寡核苷酸序列均能抑制人PBMC产生IgE，当CGTACG的寡核苷酸序列中的核心或侧翼序列被其他寡核苷酸取代时，NACGTTCG或A/CTCGTTCG序列的寡核苷酸序列能特异性地抑制人PBMC产生IgE。IFNγ和IL-12均能抑制ODN诱导的IgE产生，而抗IFN γ和抗IL-12单抗则能阻断ODN诱导的IgE产生。此外，ODNs抑制IL-4对ε生殖系转录本的诱导。我们的研究结果表明，合成ODN的施用似乎是治疗人类IgE依赖性过敏性疾病的候选治疗方法。

Syhthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs have the capacity to stimulate Th-1 responses in mice. Th-1 cytokines are known to act as down-regulators of IgE production. In this study we investigated whether synthetic ODNs inhibited IgE production in human PBMC from normal donors stimulated with interleukin-4 (IL-4) plus anti-CD40 monoclonal antibody (mAb) in vitro. Thirty-mer single-stranded ODNs were randomly selected from the cDNA encoding the MPB-70 of Mycobacterium bovis BCG.Two ODNs containing CGTACG or AAGGTT inhibited IgE production by human PBMC.When a portion of the sequence of the core or flanking oligonucleotides in the ODN containing CGTACG was substituted with other oligonucleotides, ODNs containing NACGTTCG or A/CTCGTTCG equences specifically inhibited the IgE production of human PBMC in vitro. The inhibition of IgE production by certain ODN was mediated by both IFNγ and IL-12, since the ODN-induced suppression was blocked by the addition of anti-IFNγ or anti-IL-12 mAb. Also, the ODNs inhibited the induction of the ε germ-line transcript by IL-4. Our findings indicate that the administration of synthetic ODNs appears to be a therapeutic candidate for the treatment of IgE-dependent allergic disease in humans.