Differential and competitive activation of human immune cells by distinct classes of CpG oligodeoxynucleotide

Date

2002-05-01

Author

Gürsel, Mayda
Gursel, I
Ishii, KJ
Klinman, DM

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Synthetic oligodeoxynucleotides (ODN) expressing "CpG motifs" show promise as immune adjuvants, antiallergens, anticancer, and immuno-protective agents. Two structurally distinct classes of CpG ODN have been identified that stimulate human PBMC. This work establishes that both types of ODN bind to and are internalized by the same individual B cells, NK cells, and monocytes. However, the intracellular localization of "D" and "K" ODN differs, as does their functional activity: "K" type ODN trigger monocytes and B cells to proliferate and secrete IL-6 and IgM, whereas "D" type ODN induce NK cells to produce IFN-gamma and monocytes to differentiate into CD83(+)/CD86(+) dendritic cells. In monocytes, these two types of ODN (which differ in backbone composition and CpG motif) cross-inhibit one another's activity. Thus, different types of CpG ODN have distinct and in some cases incompatible effects on the same cells, a finding with important implications for the therapeutic use of these agents.

Subject Keywords

CpG DNA, B cells, NK cells, Monocytes

URI

https://hdl.handle.net/11511/55817

Journal

JOURNAL OF LEUKOCYTE BIOLOGY

Collections

Department of Biology, Article

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Plasmacytoid Dendritic Cell Response to CpG ODN Correlates with CXCL16 Expression and Is Inhibited by ox-LDL Gürsel, Mayda; GÜRSEL, İHSAN (Hindawi Limited, 2013-01-01) Structurally distinct classes of synthetic CpG oligonucleotides (ODN) differentially activate human immune cells. K-type ODN trigger plasmacytoid dendritic cells (pDCs) to differentiate and produce TNF alpha. In contrast, D-type ODN stimulate large amounts of IFN alpha secretion from pDCs. The cell-surface receptor CXCL16 was previously shown to influence the nature and specificity of CpG ODN-induced immune activation. Here, we evaluated the expression and function of CXCL16 on pDC from healthy volunteers. ...
Sterically stabilized cationic liposomes improve the uptake and immunostimulatory activity of CpG oligonucleotides Gursel, I; Gürsel, Mayda; Ishii, KJ; Klinman, DM (The American Association of Immunologists, 2001-09-15) Immunostimulatory CpG oligonucleotides (ODN) show promise as immune adjuvants, anti-allergens, and immunoprotective agents. Increasing the bioavailability and duration of action of CpG ODN should improve their therapeutic utility. Encapsulating ODN in sterically stabilized cationic liposomes provides protection from serum nucleases while facilitating uptake by B cells, dendritic cells, and macrophages. In a pathogen challenge model, sterically stabilized cationic liposomes encapsulation doubled the duration...
Signal transduction pathways mediated by the interaction of CpG DNA with Toll-like receptor 9. Takeshita, F; Gursel, I; Ishii, KJ; Suzuki, K; Gürsel, Mayda; Klinman, DM (2004-02-01) Synthetic oligodeoxynucleotides (ODN) expressing non-methylated "CpG motifs" patterned after those present in bacterial DNA have characteristic immunomodulatory effects. CpG DNA is recognized as a pathogen-associated molecular pattern, and triggers a rapid innate immune response. CpG ODN are being harnessed for a variety of therapeutic uses, including as immune adjuvants, for cancer therapy, as anti-allergens, and as immunoprotective agents. The signal transduction pathway mediated by the engagement of CpG ...
Investigation the effect of π bridge and side chain on photovoltaic properties of benzodithiophene and quinoxaline based conjugated polymers Taşkaya Aslan, Sultan; Alemdar, Eda; Hacıefendioğlu, Tuğba; UDUM, YASEMİN; Toppare, Levent Kamil; Yıldırım, Erol; Çırpan, Ali (2022-04-15) © 2022 Elsevier LtdA series of donor–acceptor type alternative polymers containing 2D-BDT and 1D-BDT as the donors and quinoxaline as the acceptor were successfully obtained by Stille coupling reactions. Synthesized polymers containing selenophene and thiophene as π-bridges in their backbones and 2-ethylhexylselenophene and 2-ethylhexylalkoxy side groups on the BDT structure were named as P1, P2, P3 and P4, respectively. Eonsetox and Eonsetred were investigated for P1, P2, P3, and P4, respectively. Onset ox...
Activation of type I interferon-dependent genes characterizes the "core response" induced by CpG DNA. Steinhagen, F; Meyer, C; Tross, D; Gürsel, Mayda; Maeda, T; Klaschik, S; Klinman, DM (2012-10-01) Synthetic ODNs expressing CpG motifs trigger an innate immune response via TLR9. pDCs are major effectors of this response. Two structurally distinct classes of CpG ODNs have been identified that differentially activate pDCs. "K" ODNs trigger the production of TNF-alpha and IL-6, whereas "D" ODNs preferentially induce the secretion of IFN-alpha. As K and D ODNs have distinct therapeutic effects, knowledge of their shared and sequence-specific activity is of considerable importance. This work uses the CAL-1 ...

Citation Formats

M. Gürsel, I. Gursel, K. Ishii, and D. Klinman, “Differential and competitive activation of human immune cells by distinct classes of CpG oligodeoxynucleotide,” JOURNAL OF LEUKOCYTE BIOLOGY, pp. 813–820, 2002, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/55817.