Regulation of CpG-induced immune activation by suppressive oligodeoxynucleotides

被引:29
作者
Klinman, DM [1 ]
Zeuner, R [1 ]
Yamada, H [1 ]
Gursel, M [1 ]
Currie, D [1 ]
Gursel, I [1 ]
机构
[1] US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Res, Bethesda, MD 20892 USA
来源
THERAPEUTIC OLIGONUCLEOTIDES: ANTISENSE, RNAI, TRIPLE-HELIX, GENE REPAIR, ENHANCER DECOYS, CPG AND DNA CHIPS | 2003年 / 1002卷
关键词
synthetic oligonucleotides; CpG motifs; immune activation;
D O I
10.1196/annals.1281.023
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated "CpG motifs" stimulate an innate immune response characterized by the production of cytokines, chemokines, and polyreactive Igs that promote host survival following infectious challenge. Yet CpG-driven immune activation can have deleterious consequences, such as increasing the host's susceptibility to autoimmune disease. The immunomodulatory activity of CpG DNA can be blocked by DNA containing "suppressive" motifs. This work explores the rules governing cellular recognition of stimulatory and suppressive motifs, and the resultant modulation of the immune system. Results suggest that both CpG and suppressive ODN may find use as therapeutic agents.
引用
收藏
页码:112 / 123
页数:12
相关论文
共 42 条
[21]   Sequence motifs in adenoviral DNA block immune activation by stimulatory CpG motifs [J].
Krieg, AM ;
Wu, T ;
Weeratna, R ;
Efler, SM ;
Love-Homan, L ;
Yang, L ;
Yi, AK ;
Short, D ;
Davis, HL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (21) :12631-12636
[22]  
Krieg AM, 1998, J IMMUNOL, V161, P2428
[23]   The role of CpG motifs in innate immunity [J].
Krieg, AM .
CURRENT OPINION IN IMMUNOLOGY, 2000, 12 (01) :35-43
[24]   CpG stimulation of primary mouse B cells is blocked by inhibitory oligodeoxyribonucleotides at a site proximal to NF-κB activation [J].
Lenert, P ;
Stunz, L ;
Yi, AK ;
Krieg, AM ;
Ashman, RF .
ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT, 2001, 11 (04) :247-256
[25]   TETRAPLEX FOLDING OF TELOMERE SEQUENCES AND THE INCLUSION OF ADENINE BASES [J].
MURCHIE, AIH ;
LILLEY, DMJ .
EMBO JOURNAL, 1994, 13 (04) :993-1001
[26]   Immunological properties of bacterial DNA [J].
Pisetsky, DS ;
Reich, C ;
Crowley, SD ;
Halpern, MD .
DNA VACCINES: A NEW ERA IN VACCINOLOGY, 1995, 772 :152-163
[27]   Immunostimulatory DNA: A clear and present danger? [J].
Pisetsky, DS .
NATURE MEDICINE, 1997, 3 (08) :829-831
[28]   Immunostimulatory DNA sequences function as T helper-1-promoting adjuvants [J].
Roman, M ;
MartinOrozco, E ;
Goodman, S ;
Nguyen, MD ;
Sato, Y ;
Ronaghy, A ;
Kornbluth, RS ;
Richman, DD ;
Carson, DA ;
Raz, E .
NATURE MEDICINE, 1997, 3 (08) :849-854
[29]   CPG oligonucleotides are potent adjuvants for the activation of autoreactive encephalitogenic T cells in vivo [J].
Segal, BM ;
Chang, JT ;
Shevach, EM .
JOURNAL OF IMMUNOLOGY, 2000, 164 (11) :5683-5688
[30]  
Sparwasser T, 1998, EUR J IMMUNOL, V28, P2045, DOI 10.1002/(SICI)1521-4141(199806)28:06<2045::AID-IMMU2045>3.0.CO