PyNTTTTGT and CpG immunostimulatory oligonucleotides: effect on granulocyte/monocyte colony-stimulating factor (GM-CSF) secretion by human CD56+ (NK and NKT) cells

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) w...

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Veröffentlicht in:PloS one 2015-02, Vol.10 (2), p.e0117484-e0117484
Hauptverfasser: Rodriguez, Juan M, Marchicio, José, López, Mariela, Ziblat, Andrea, Elias, Fernanda, Fló, Juan, López, Ricardo A, Horn, David, Zorzopulos, Jorge, Montaner, Alejandro D
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container_title PloS one
container_volume 10
creator Rodriguez, Juan M
Marchicio, José
López, Mariela
Ziblat, Andrea
Elias, Fernanda
Fló, Juan
López, Ricardo A
Horn, David
Zorzopulos, Jorge
Montaner, Alejandro D
description 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.
doi_str_mv 10.1371/journal.pone.0117484
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Keith</contributor><creatorcontrib>Rodriguez, Juan M ; Marchicio, José ; López, Mariela ; Ziblat, Andrea ; Elias, Fernanda ; Fló, Juan ; López, Ricardo A ; Horn, David ; Zorzopulos, Jorge ; Montaner, Alejandro D ; Reeves, R. Keith</creatorcontrib><description>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. 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metabolism</topic><topic>Granulocytes</topic><topic>Humans</topic><topic>Immune system</topic><topic>Immunostimulation</topic><topic>Infections</topic><topic>Inhibition</topic><topic>Interference</topic><topic>Interferon</topic><topic>Interferon-alpha - metabolism</topic><topic>Interferon-gamma - metabolism</topic><topic>Interleukin</topic><topic>Interleukin 2</topic><topic>Interleukin-2 - pharmacology</topic><topic>Interleukin-8 - metabolism</topic><topic>Killer Cells, Natural - drug effects</topic><topic>Killer Cells, Natural - metabolism</topic><topic>Leukocytes (granulocytic)</topic><topic>Leukocytes (mononuclear)</topic><topic>Lymphocytes</topic><topic>Monocytes</topic><topic>Natural Killer T-Cells - drug effects</topic><topic>Natural Killer T-Cells - metabolism</topic><topic>Oligodeoxyribonucleotides - pharmacology</topic><topic>Oligonucleotides</topic><topic>Peripheral blood mononuclear cells</topic><topic>Signal transduction</topic><topic>T cell receptors</topic><topic>TLR9 protein</topic><topic>Toll-like receptors</topic><topic>Tumor Necrosis Factor-alpha - 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Keith</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PyNTTTTGT and CpG immunostimulatory oligonucleotides: effect on granulocyte/monocyte colony-stimulating factor (GM-CSF) secretion by human CD56+ (NK and NKT) cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-02-23</date><risdate>2015</risdate><volume>10</volume><issue>2</issue><spage>e0117484</spage><epage>e0117484</epage><pages>e0117484-e0117484</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><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. 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subjects CD56 antigen
Colonies
Colony-stimulating factor
CpG islands
Cytokines
Dendritic cells
Granulocyte-macrophage colony-stimulating factor
Granulocyte-Macrophage Colony-Stimulating Factor - metabolism
Granulocytes
Humans
Immune system
Immunostimulation
Infections
Inhibition
Interference
Interferon
Interferon-alpha - metabolism
Interferon-gamma - metabolism
Interleukin
Interleukin 2
Interleukin-2 - pharmacology
Interleukin-8 - metabolism
Killer Cells, Natural - drug effects
Killer Cells, Natural - metabolism
Leukocytes (granulocytic)
Leukocytes (mononuclear)
Lymphocytes
Monocytes
Natural Killer T-Cells - drug effects
Natural Killer T-Cells - metabolism
Oligodeoxyribonucleotides - pharmacology
Oligonucleotides
Peripheral blood mononuclear cells
Signal transduction
T cell receptors
TLR9 protein
Toll-like receptors
Tumor Necrosis Factor-alpha - metabolism
Tumor necrosis factor-α
γ-Interferon
title PyNTTTTGT and CpG immunostimulatory oligonucleotides: effect on granulocyte/monocyte colony-stimulating factor (GM-CSF) secretion by human CD56+ (NK and NKT) cells
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