Differential and competitive activation of human immune cells by distinct classes of CpG oligodeoxynucleotide.
Synthetic oligodeoxynucleotides (ODN) expressing "CpG motifs" show promise as immune adjuvants, antiallergens, anticancer, and immunoprotective 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.
Gürsel
Mayda
M
Section of Retroviral Research, Center for Biologics Evaluation and Research, Food and Drug Administration, Bldg. 29A Rm. 3D10, 8800 Rockville Pike, Bethesda, MD 20892, USA.
Verthelyi
Daniela
D
Gürsel
Ihsan
I
Ishii
Ken J
KJ
Klinman
Dennis M
DM
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D004705:Endocytosis; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000145:classification / Q000378:metabolism / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides