APC stimulated by CpG oligodeoxynucleotide enhance activation of MHC class I-restricted T cells.
Oligonucleotides containing unmethylated CpG motifs (cytosine-phosphorothioate-guanine oligodeoxynucleotide (CpG ODN)) are potent immunostimulatory agents capable of enhancing the Ag-specific Th1 response when used as immune adjuvants. We evaluated the cellular mechanisms responsible for this effect. Development of a CTL response was enhanced when mice were immunized with peptide-pulsed dendritic cells (DCs) treated with CpG ODN. However, in vitro, CpG ODN had no direct effect on highly purified T cells. In vitro, CpG ODN treatment of peptide- or protein-pulsed DCs enhanced the ability of the DCs to activate class I-restricted T cells. The presence of helper T cells enhanced this effect, indicating that treatment with CpG ODN does not obviate the role of T cell help. The enhanced ability of CpG ODN-treated DCs to activate T cells was present but blunted when DCs derived from IL-12 knockout mice were used. Fixation of Ag-pulsed, CpG ODN-treated DCs limited their ability to activate T cells. In contrast, fixation had little effect on DC activation of T cells when DCs were not exposed to CpG ODN. This indicates that production of soluble factors by DCs stimulated with CpG ODN plays a particularly important role in their ability to activate class I-restricted T cells. We conclude that CpG ODN enhances the development of a cellular immune response by stimulating APCs such as DCs, to produce IL-12 and other soluble factors.
Warren
T L
TL
The Holden Cancer Center and Departments of Internal Medicine and Urology, University of Iowa, Iowa City, IA 522421, USA.
Bhatia
S K
SK
Acosta
A M
AM
Dahle
C E
CE
Ratliff
T L
TL
Krieg
A M
AM
Weiner
G J
GJ
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004527:Egg Proteins / Q000276:immunology / Q000494:pharmacology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D018664:Interleukin-12 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides / Q000276:immunology* / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D010446:Peptide Fragments; D012995:Solubility; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D016207:Cytokines; D004527:Egg Proteins; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; C110366:OVA-8; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D018664:Interleukin-12; D010047:Ovalbumin