Human Peripheral Blood Cells Differentially Recognize and Respond to Two Distinct CpG Motifs

Oligodeoxynucleotides (ODN) that contain unmethylated CpG dinucleotides trigger a strong innate immune response in vertebrates. CpG ODN show promise as vaccine adjuvants, anti-allergens, and immunoprotective agents in animal models. Their transition to clinical use requires the identification of mot...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2001-02, Vol.166 (4), p.2372-2377
Main Authors: Verthelyi, Daniela, Ishii, Ken J, Gursel, Mayda, Takeshita, Fumihiko, Klinman, Dennis M
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - chemistry
Adjuvants, Immunologic - pharmacology
B-Lymphocytes - immunology
B-Lymphocytes - metabolism
Cell Division - immunology
Cell Line
CpG Islands - immunology
Dendritic Cells - immunology
Dendritic Cells - metabolism
Humans
Immunoglobulin M - biosynthesis
Interferon-gamma - metabolism
Interleukin-6 - metabolism
Killer Cells, Natural - immunology
Killer Cells, Natural - metabolism
Leukocytes, Mononuclear - cytology
Leukocytes, Mononuclear - immunology
Leukocytes, Mononuclear - metabolism
Lymphocyte Activation - immunology
Monocytes - immunology
Monocytes - metabolism
Oligodeoxynucleotides
Oligodeoxyribonucleotides - chemistry
Oligodeoxyribonucleotides - pharmacology
Tumor Cells, Cultured
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Summary:Oligodeoxynucleotides (ODN) that contain unmethylated CpG dinucleotides trigger a strong innate immune response in vertebrates. CpG ODN show promise as vaccine adjuvants, anti-allergens, and immunoprotective agents in animal models. Their transition to clinical use requires the identification of motifs that are optimally stimulatory in humans. Analysis of hundreds of novel ODN resulted in the identification and characterization of two structurally distinct "clusters" of immunostimulatory CpG ODN. One cluster ("D") preferentially stimulates IFN-gamma production by NK cells, whereas the other ("K") stimulates cell proliferation and the production of IL-6 and IgM by monocytes and B cells. The distinct immunostimulatory properties of K and D ODN can improve the design of CpG-based products to achieve specific therapeutic goals.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.166.4.2372