title: PyNTTTTGT and CpG immunostimulatory oligonucleotides: effect on granulocyte/monocyte colony-stimulating factor (GM-CSF) secretion by human CD56+ (NK and NKT) cells.
abstract: CD56+ cells have been recognized as being involved in bridging the innate and acquired immune systems. Herein, we assessed the effect of two major classes of immunostimulatory oligonucleotides (ODNs), PyNTTTTGT and CpG, on CD56+ cells. Incubation of human peripheral blood mononuclear cells (hPBMC) with some of these ODNs led to secretion of significant amounts of interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α) and granulocyte/monocyte colony-stimulating factor (GM-CSF), but only if interleukin 2 (IL2) was present. IMT504, the prototype of the PyNTTTTGT ODN class, was the most active. GM-CSF secretion was very efficient when non-CpG ODNs with high T content and PyNTTTTGT motifs lacking CpGs were used. On the other hand, CpG ODNs and IFNα inhibited this GM-CSF secretion. Selective cell type removal from hPBMC indicated that CD56+ cells were responsible for GM-CSF secretion and that plasmacytoid dendritic cells (PDCs) regulate this process. In addition, PyNTTTTGT ODNs inhibited the IFNα secretion induced by CpG ODNs in PDCs by interference with the TLR9 signaling pathway. Since IFNα is essential for CD56+ stimulation by CpG ODNs, there is a reciprocal interference of CpG and PyNTTTTGT ODNs when acting on this cell population. This suggests that these synthetic ODNs mimic different natural alarm signals for activation of the immune system.
authors.affiliation: Fundación Pablo Cassará, Buenos Aires, Argentina.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Rodriguez
authors.affiliation: Immunotech S.A., Buenos Aires, Argentina.
authors.forename: José
authors.initials: J
authors.lastname: Marchicio
authors.affiliation: Immunotech S.A., Buenos Aires, Argentina.
authors.forename: Mariela
authors.initials: M
authors.lastname: López
authors.affiliation: Immunotech S.A., Buenos Aires, Argentina.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ziblat
authors.affiliation: Immunotech S.A., Buenos Aires, Argentina.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Elias
authors.affiliation: Immunotech S.A., Buenos Aires, Argentina.
authors.forename: Juan
authors.initials: J
authors.lastname: Fló
authors.affiliation: Immunotech S.A., Buenos Aires, Argentina.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: López
authors.affiliation: David Horn LLC, Doylestown, Pennsylvania, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Horn
authors.affiliation: Immunotech S.A., Buenos Aires, Argentina.
authors.forename: Jorge
authors.initials: J
authors.lastname: Zorzopulos
authors.affiliation: Instituto de Ciencia y Tecnología "Dr. Cesar Milstein", Buenos Aires, Argentina.
authors.forename: Alejandro D
authors.initials: AD
authors.lastname: Montaner
mesh_terms: D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000187:drug effects* / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C408982:CPG-oligonucleotide; C514285:IMT504; D016898:Interferon-alpha; D007376:Interleukin-2; D016209:Interleukin-8; D009838:Oligodeoxyribonucleotides; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor