CpG oligodeoxynucleotides induce human monocytes to mature into functional dendritic cells.
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 up-regulation 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.
Gursel
Mayda
M
Section of Retroviral Immunology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda 20892, USA.
Verthelyi
Daniela
D
Klinman
Dennis M
DM
D000818:Animals; D000917:Antibody Formation; D017951:Antigen Presentation; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D018920:Coculture Techniques; D018899:CpG Islands; D004269:DNA, Bacterial / Q000737:chemistry; D004279:DNA, Viral / Q000737:chemistry; D003713:Dendritic Cells / Q000145:classification / Q000166:cytology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007111:Immunity, Cellular; D007156:Immunologic Memory; D016898:Interferon-alpha / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology; D051379:Mice; D016513:Mice, SCID; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D010047:Ovalbumin / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology / Q000494:pharmacology
D015703:Antigens, CD; D004269:DNA, Bacterial; D004279:DNA, Viral; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; D013745:Tetanus Toxoid; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010047:Ovalbumin