PMID- 10430938 OWN - NLM STAT- MEDLINE DCOM- 19990909 LR - 20190501 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 96 IP - 16 DP - 1999 Aug 3 TI - CpG DNA: a potent signal for growth, activation, and maturation of human dendritic cells. PG - 9305-10 AB - 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. FAU - Hartmann, G AU - Hartmann G AD - Department of Internal Medicine and the University of Iowa Cancer Center, University of Iowa, Iowa City, IA 52242, USA. FAU - Weiner, G J AU - Weiner GJ FAU - Krieg, A M AU - Krieg AM LA - eng GR - DK25295/DK/NIDDK NIH HHS/United States GR - P01CA66570/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Adjuvants, Immunologic) RN - 0 (Antigens, CD) RN - 0 (Dinucleoside Phosphates) RN - 0 (HLA-D Antigens) RN - 0 (Lipopolysaccharides) RN - 0 (Oligodeoxyribonucleotides) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 2382-65-2 (cytidylyl-3'-5'-guanosine) RN - 9007-49-2 (DNA) SB - IM MH - Adjuvants, Immunologic MH - Animals MH - Antigens, CD/analysis MH - B-Lymphocytes/immunology MH - Base Sequence MH - Cells, Cultured MH - DNA/*immunology MH - DNA Methylation MH - Dendritic Cells/*cytology/drug effects/*immunology MH - Dinucleoside Phosphates/*immunology MH - Flow Cytometry MH - Gene Expression Regulation MH - Genes, MHC Class II MH - HLA-D Antigens/genetics MH - Humans MH - Intercellular Adhesion Molecule-1/genetics MH - Killer Cells, Natural/immunology MH - Lipopolysaccharides/pharmacology MH - Lymphocyte Activation MH - Lymphocyte Culture Test, Mixed MH - Mice MH - Oligodeoxyribonucleotides/*immunology MH - Signal Transduction/*immunology MH - Th1 Cells/immunology MH - Th2 Cells/immunology PMC - PMC17777 EDAT- 1999/08/04 00:00 MHDA- 1999/08/04 00:01 PMCR- 2000/02/03 CRDT- 1999/08/04 00:00 PHST- 1999/08/04 00:00 [pubmed] PHST- 1999/08/04 00:01 [medline] PHST- 1999/08/04 00:00 [entrez] PHST- 2000/02/03 00:00 [pmc-release] AID - 2280 [pii] AID - 10.1073/pnas.96.16.9305 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9305-10. doi: 10.1073/pnas.96.16.9305.