CpG-A and CpG-B oligonucleotides differentially enhance human peptide-specific primary and memory CD8+ T-cell responses in vitro.
Two distinct types of CpG oligodeoxynucleotide (ODN) have been identified that differ in their capacity to stimulate antigen-presenting cells: CpG-A induces high amounts of interferon-alpha (IFN-alpha) and IFN-beta in plasmacytoid dendritic cells (PDCs), whereas CpG-B induces PDC maturation and is a potent activator of B cells but stimulates only small amounts of IFN-alpha and IFN-beta. Here we examined the ability of these CpG ODNs to enhance peptide-specific CD8+ T-cell responses in human peripheral blood mononuclear cells (PBMCs). The frequency of influenza matrix-specific "memory" CD8+ T cells was increased by both types of CpG ODN, whereas the frequency of Melan-A specific "naive" CD8+ T cells increased on stimulation with CpG-B but not with CpG-A. The presence of PDCs in PBMCs was required for this CpG ODN-mediated effect. The expanded cells were cytotoxic and produced IFN- on peptide restimulation. Soluble factors induced by CpG-A but not CpG-B increased the granzyme-B content and cytotoxicity of established CD8+ T-cell clones, each of which was IFN-alpha/-beta dependent. In conclusion, CpG-B seems to be superior for priming CD8+ T-cell responses, and CpG-A selectively enhances memory CD8+ T-cell responses and induces cytotoxicity. These results demonstrate distinct functional properties of CpG-A and CpG-B with regard to CD8 T cells.
Rothenfusser
Simon
S
Department of Internal Medicine, Division of Clinical Pharmacology, University of Munich, Germany.
Hornung
Veit
V
Ayyoub
Maha
M
Britsch
Stefanie
S
Towarowski
Andreas
A
Krug
Anne
A
Sarris
Anja
A
Lubenow
Norbert
N
Speiser
Daniel
D
Endres
Stefan
S
Hartmann
Gunther
G
D000951:Antigens, Neoplasm; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018899:CpG Islands; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000502:physiology*; D016130:Immunophenotyping; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D058965:MART-1 Antigen; D009363:Neoplasm Proteins / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000276:immunology
D000951:Antigens, Neoplasm; C408982:CPG-oligonucleotide; D016898:Interferon-alpha; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D014763:Viral Matrix Proteins; C098952:influenza virus membrane protein (58-66); D016899:Interferon-beta; D007371:Interferon-gamma