Synthetic Oligodeoxynucleotides Inhibit IgE Induction in Human Lymphocytes

Abstract

Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs have the capacity to stimulate T-helper (Th)1-type responses in mice. Th1 cytokines are known to act as downregulators of IgE production. In this study we investigated whether synthetic ODNs inhibited IgE production in human peripheral blood mononuclear cells (PBMC) from normal donors stimulated with interleukin (IL)-4 plus anti-CD40 monoclonal antibody (mAb) in vitro. Thirty-mer single-stranded ODNs were randomly selected from the complementary DNA encoding the MPB-70 of Mycobacterium bovis Bacillus Calmette-Guerin. Two ODNs, containing CGTACG or AACGTT inhibited IgE production by human PBMC. When other oligonucleotides were substituted in a portion of the sequence of the core or flanking oligonucleotides in the ODN containing CGTACG, ODNs containing NACGTTCG or A/CTCGTTCG sequences specifically inhibited IgE production by human PBMC in vitro. The inhibition of IgE production by certain ODNs was mediated by both interferon (IFN)-gamma and IL-12, since the ODN-induced suppression was blocked by the addition of anti-IFN-gamma or anti-IL-12 mAb. Also, the ODNs inhibited induction of epsilon germline transcripts by IL-4. Our findings indicate that synthetic ODNs appear to be candidates for the treatment of IgE-dependent allergic disease in humans.