CpG oligodeoxynucleotides induce human monocytes to mature into functional dendritic cells.

Date

2002-09-01

Author

Gürsel, Mayda
Klinman, DM

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Dendritic cells (DC) excel at presenting antigen to T cells and thus make a key contribution to the induction of primary and secondary immune responses. DC matured in vitro and pulsed with antigen show promise for the immunotherapy of cancer and infectious diseases. Synthetic oligonucleotides (ODN) expressing immunomodulatory "CpG motifs" were found to boost APC function in mice. Current results demonstrate that the recently identified "D" type of CpG ODN stimulate human peripheral blood monocytes to mature into functionally active DC over 2-4 days. The transition from monocyte to DC is characterized by the upregulation of CD83, CD86, CD80, CD40 and the down-regulation of CD14. These DC support antigen-specific humoral and cellular responses in vitro and in vivo. The differentiation of these monocytes is mediated by plasmacytoid DC, which respond to D type ODN by secreting IFN-alpha. Since D type CpG motifs are present in bacterial and viral DNA, the maturation of monocytes into functional DC may reflect a physiologic response that can be harnessed therapeutically through the use of CpG ODN.

Subject Keywords

CpG oligodeoxynucleotide, Monocyte, Dendritic cell, Maturation, Human

URI

https://hdl.handle.net/11511/38267

Journal

European journal of immunology

DOI

https://doi.org/10.1002/1521-4141(200209)32:9<2617::aid-immu2617>3.0.co;2-f

Collections

Department of Biology, Article

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CpG DNA: recognition by and activation of monocytes. Klinman, DM; Takeshita, F; Gursel, I; Leifer, C; Ishii, KJ; Verthelyi, D; Gürsel, Mayda (2002-07-01) Unmethylated CpG motifs present in bacterial DNA rapidly trigger an innate immune response characterized by the activation of Ig- and cytokine-secreting cells. Synthetic oligonucleotides (ODNs) containing CpG motifs mimic this activity, triggering monocytes to proliferate, secrete and/or differentiate. Analysis of hundreds of novel ODNs led to the identification of two structurally distinct classes of CpG motif that differentially activate human monocytes. ODNs of the "K"-type interact with Toll-like recept...
CpG oligodeoxynucleotides protect normal and SIV-infected macaques from Leishmania infection. Verthelyi, D; Gürsel, Mayda; Kenney, RT; Lifson, JD; Liu, S; Mican, J; Klinman, DM (The American Association of Immunologists, 2003-05-01) Oligodeoxynucleotides containing CpG motifs (CpG ODNs) mimic microbial DNA and activate effectors of the innate immune response, which limits the spread of pathogens and promotes an adaptive immune response. CpG ODNs have been shown to protect mice from infection with intracellular pathogens. Unfortunately, CpG motifs that optimally stimulate humans are only weakly active in mice, mandating the use of nonhuman primates to monitor the activity and safety of "human" CpG ODNs in vivo. This study demonstrates t...
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Citation Formats

M. Gürsel and D. Klinman, “CpG oligodeoxynucleotides induce human monocytes to mature into functional dendritic cells.,” European journal of immunology, pp. 2617–22, 2002, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/38267.