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.
Highlights
Immunostimulatory oligonucleotides (ODNs) can be classified in two major classes: a) CpG ODNs, which contain at least one CpG motif in their sequence [1] and b) PyNTTTTGTPLOS ONE | DOI:10.1371/journal.pone.0117484 February 23, 2015PyNTTTTGT and CpG ODNs: Effect on granulocyte/monocyte colony-stimulating factor (GM-CSF) Secretion respectively, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript
CD56+ cells are the main cells responsible for GM-CSF secretion induced by PyNTTTTGT ODNs in human peripheral blood mononuclear cells (hPBMC) and, according to flow cytometry analysis, they are loaded with GM-CSF after incubation with interleukin 2 (IL2), a well-known inducer of the GM-CSF gene transcription in Natural Killer (NK) cells [28]
CpG ODNs and IFNα inhibited the GM-CSF secretion induced by PyNTTTTGT ODNs in hPBMC, and IFNα inhibited the ODN-induced secretion of this cytokine in purified CD56+ cells
Summary
Immunostimulatory oligonucleotides (ODNs) can be classified in two major classes: a) CpG ODNs, which contain at least one CpG motif in their sequence [1] and b) PyNTTTTGTPLOS ONE | DOI:10.1371/journal.pone.0117484 February 23, 2015PyNTTTTGT and CpG ODNs: Effect on GM-CSF Secretion respectively, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Immunostimulatory oligonucleotides (ODNs) can be classified in two major classes: a) CpG ODNs, which contain at least one CpG motif in their sequence [1] and b) PyNTTTTGT. PyNTTTTGT and CpG ODNs: Effect on GM-CSF Secretion respectively, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the author contributions section
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
