CpG DNA: A potent signal for growth, activation, and maturation of human dendritic cells

G Hartmann; G. J Weiner; A. M Krieg

doi:10.1073/pnas.96.16.9305

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CpG DNA: A potent signal for growth, activation, and maturation of human dendritic cells

Journal article

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CpG DNA: A potent signal for growth, activation, and maturation of human dendritic cells

G Hartmann, G. J Weiner and A. M Krieg

Proceedings of the National Academy of Sciences - PNAS, Vol.96(16), pp.9305-9310

08/03/1999

DOI: 10.1073/pnas.96.16.9305

PMCID: PMC17777

PMID: 10430938

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Abstract

DNA molecules containing unmethylated CpG-dinucleotides in particular base contexts (“CpG motifs”) are excellent adjuvants in rodents, but their effects on human cells have been less clear. Dendritic cells (DCs) form the link between the innate and the acquired immune system and may influence the balance between T helper 1 (Th1) and Th2 immune responses. We evaluated the effects of CpG oligodeoxynucleotides alone or in combination with granulocyte–macrophage colony-stimulating factor (GMCSF) on different classes of purified human DCs. For primary dendritic precursor cells isolated from human blood, CpG oligonucleotides alone were superior to GMCSF in promoting survival and maturation (CD83 expression) as well as expression of class II MHC and the costimulatory molecules CD40, CD54, and CD86 of DCs. Both CD4-positive and CD4-negative peripheral blood dendritic precursor cells responded to CpG DNA which synergized with GMCSF but these DCs showed little response to lipopolysaccharide (LPS). In contrast, monocyte-derived DCs did not respond to CpG, but they were highly sensitive to LPS, suggesting an inverse correlation between CpG and LPS sensitivity in different subsets of DCs. Compared with GMCSF, CpG-treated peripheral blood DCs showed enhanced functional activity in the mixed lymphocyte reaction and induced T cells to secrete increased levels of Th1 cytokines. These findings demonstrate the ability of specific CpG motifs to strongly activate certain subsets of human DCs to promote Th1-like immune responses, and support the use of CpG DNA-based trials for immunotherapy against cancer, allergy, and infectious diseases.

Biological Sciences

adjuvant

therapeutic DNA

oligodeoxynucleotide

immunotherapy

Details

Title: Subtitle: CpG DNA: A potent signal for growth, activation, and maturation of human dendritic cells
Creators: G Hartmann - Department of Internal Medicine and the University of Iowa Cancer Center, University of Iowa, Iowa City, IA 52242
G. J Weiner - Department of Internal Medicine and the University of Iowa Cancer Center, University of Iowa, Iowa City, IA 52242
A. M Krieg - Department of Internal Medicine and the University of Iowa Cancer Center, University of Iowa, Iowa City, IA 52242
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.96(16), pp.9305-9310
DOI: 10.1073/pnas.96.16.9305
PMID: 10430938
PMCID: PMC17777
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 08/03/1999
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Internal Medicine
Record Identifier: 9984094724902771

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