Effect of suppressive DNA on CpG-induced immune activation.
Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs stimulate a strong innate immune response. This stimulation can be abrogated by either removing the CpG DNA or adding inhibitory/suppressive motifs. Suppression is dominant over stimulation and is specific for CpG-induced immune responses (having no effect on LPS- or Con A-induced activation). Individual cells noncompetitively internalize both stimulatory and suppressive ODN. Studies using ODN composed of both stimulatory and suppressive motifs indicate that sequence recognition proceeds in a 5'-->3' direction, and that a 5' motif can block recognition of immediately 3' sequences. These findings contribute to our understanding of the immunomodulatory activity of DNA-based products and the rules that govern immune recognition of stimulatory and suppressive motifs.
Yamada
Hiroshi
H
Section of Retroviral Immunology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Gursel
Ihsan
I
Takeshita
Fumihiko
F
Conover
Jackie
J
Ishii
Ken J
KJ
Gursel
Mayda
M
Takeshita
Saoko
S
Klinman
Dennis M
DM
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D018899:CpG Islands / Q000276:immunology*; D004247:DNA / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000378:metabolism / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013491:Suppressor Factors, Immunologic / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D009838:Oligodeoxyribonucleotides; D013491:Suppressor Factors, Immunologic; D018664:Interleukin-12; D007371:Interferon-gamma; D004247:DNA