Journal article
Highly Immunostimulatory CpG-Free Oligodeoxynucleotides for Activation of Human Leukocytes
Antisense & nucleic acid drug development, Vol.12(3), pp.165-175
06/2002
DOI: 10.1089/108729002760220761
PMID: 12162699
Abstract
Synthetic oligodeoxynucleotides (ODNs) bearing CpG dinucleotides can mimic the immunostimulatory effects of bacterial DNA in vertebrates. Besides the known CpG motifs, no other sequence motif has been shown to have independent immunostimulatory effects. Several past investigators have demonstrated that the nucleotide content or the phosphorothioate (PS) backbone may have effects independently of the sequence. However, the effect of both nucleotide content and PS backbone to stimulate human leukocytes is not well understood. We investigated the immunostimulatory activity of 34 PS-ODNs with different nucleotide contents, lengths, and methylation status on human leukocytes. The thymidine content showed strong CpG-independent contribution to immunostimulation. In contrast, ODNs rich in other nucleotides (guanosine, cytosine, or adenosine) induced no or much lower levels of immunostimulation. The observed effects were highly dependent on the PS backbone chemistry. In addition to the base content and the backbone chemistry, the length of the PS-ODN was directly related to the magnitude of its stimulatory effects, especially on B cells. In addition, methylation of CpG dinucleotides did not always cause an abrogation of the immunostimulation. Immunostimulatory effects could be observed with methylated CpG ODNs, specifically as the ODN length was increased from 18 to 24 or more nucleotides (nt). In contrast, PS-ODNs with inverted CpG dinucleotides showed some but only weak immunostimulation. Our results demonstrate that non-CpG ODNs rich in thymidine or ODNs with methylated CpG motifs have length-dependent immunostimulatory effects. Such ODNs can induce effects similar to those seen with CpG ODNs but are much less efficient in stimulating human immune cells.
Details
- Title: Subtitle
- Highly Immunostimulatory CpG-Free Oligodeoxynucleotides for Activation of Human Leukocytes
- Creators
- Jörg Vollmer - Coley Pharmaceutical GmbH, Langenfeld, Germany, Coley Pharmaceutical Group, Wellesley, MA 02481Andrea Janosch - Coley Pharmaceutical GmbH, Langenfeld, Germany, Coley Pharmaceutical Group, Wellesley, MA 02481Meike Laucht - Coley Pharmaceutical GmbH, Langenfeld, Germany, Coley Pharmaceutical Group, Wellesley, MA 02481Zuhair K Ballas - Department of Veterans Affairs Medical Center, Iowa City, IA 52246, and Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242Christian Schetter - Coley Pharmaceutical GmbH, Langenfeld, Germany, Coley Pharmaceutical Group, Wellesley, MA 02481Arthur M Krieg - Coley Pharmaceutical GmbH, Langenfeld, Germany, Coley Pharmaceutical Group, Wellesley, MA 02481, Department of Veterans Affairs Medical Center, Iowa City, IA 52246, and Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- Antisense & nucleic acid drug development, Vol.12(3), pp.165-175
- DOI
- 10.1089/108729002760220761
- PMID
- 12162699
- ISSN
- 1087-2906
- eISSN
- 2168-6599
- Language
- English
- Date published
- 06/2002
- Academic Unit
- Immunology; Internal Medicine
- Record Identifier
- 9984094761802771
Metrics
8 Record Views