Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA

Zuhair K Ballas; Wendy L Rasmussen; Arthur M Krieg

doi:10.4049/jimmunol.157.5.1840

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Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA

Journal article

Peer reviewed

Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA

Zuhair K Ballas, Wendy L Rasmussen and Arthur M Krieg

The Journal of immunology (1950), Vol.157(5), pp.1840-1845

09/01/1996

DOI: 10.4049/jimmunol.157.5.1840

PMID: 8757300

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Abstract

We have recently shown that oligodeoxynucleotides (ODN) containing unmethylated CpG dinucleotides (CpG motif) can induce B cells to proliferate, differentiate, and secrete cytokines. In this study we demonstrate that CpG motifs contained in ODN as short as 15 bases in length were quite effective at inducing NK cell lytic activity in vitro in both human and murine lymphocytes. Such ODN were also effective at inducing NK lytic activity, in vivo, in mice. Experiments designed to determine the cellular and cytokine requirements for NK cell induction revealed that B and T cells are not necessary, that the ODN do not augment the activity of highly purified NK cells, and that the ODN augment NK cell activity indirectly by inducing the secretion of IL-12, IFN-alpha beta, and TNF-alpha. Various ODN sequences were prepared to determine the optimal ODN length, motif, palindrome, backbone modification, and dose requirements. We found no requirement for a palindromic sequence but a definite requirement for an unmethylated CpG motif. While necessary, however, a CpG motif was not sufficient for NK cell induction. Instead, there appeared to be stringent requirements for the immediate flanking bases at the 5' and 3' ends as well as for flanking sequences outside the immediate 5' and 3' bases. In particular poly(G) ends seemed to exert a complex qualitative and quantitative effect which could be up- or down-modulating depending on whether the ODN backbone was phosphorothioate modified or not.

DNA, Bacterial - pharmacology

Oligodeoxyribonucleotides - administration & dosage

Humans

Oligodeoxyribonucleotides - chemistry

Dinucleoside Phosphates - chemistry

Base Sequence

Killer Cells, Natural - immunology

Mice, Inbred DBA

DNA, Bacterial - administration & dosage

Interferon Type I - physiology

Cytotoxicity, Immunologic - drug effects

Mice, Inbred C57BL

Injections, Intraperitoneal

Mice, SCID

Animals

B-Lymphocytes - immunology

Lymphocyte Activation - drug effects

Mice, Nude

Interleukin-12 - immunology

Tumor Necrosis Factor-alpha - physiology

T-Lymphocytes - immunology

Mice

Mice, Inbred BALB C

Dinucleoside Phosphates - pharmacology

Oligodeoxyribonucleotides - pharmacology

Dinucleoside Phosphates - administration & dosage

Details

Title: Subtitle: Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA
Creators: Zuhair K Ballas - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA
Wendy L Rasmussen
Arthur M Krieg
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.157(5), pp.1840-1845
DOI: 10.4049/jimmunol.157.5.1840
PMID: 8757300
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: R29-AR42556-01 / NIAMS NIH HHS
Language: English
Date published: 09/01/1996
Academic Unit: Immunology; Internal Medicine
Record Identifier: 9984094746602771

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