Oligodeoxynucleotides containing CpG motifs induce low levels of TNF-alpha in human B lymphocytes: possible adjuvants for Th1 responses.
Oligodeoxynucleotides containing CpG motifs (CpG-ODN) represent potential adjuvants for specific immunotherapy of type I allergies because they foster Th1-like immune responses. However, previous work has shown that CpG-ODN induce systemically active levels of TNF-alpha in murine macrophages. The goal of the present study was to evaluate the release of TNF-alpha in human cells by a CpG-ODN proven to induce Th1 immune responses in cells from atopic individuals and in mice. CpG-ODN induced TNF-alpha in cells from atopic and healthy individuals. However, the amounts were low, as determined by comparison with commonly used Ags. Intracellular cytokine staining of PBMC revealed that CpG-ODN-induced TNF-alpha derived exclusively from B lymphocytes. TNF-alpha contributed to the CpG-ODN-augmented proliferation and Ig synthesis in PBMC, but was not involved in IFN-gamma synthesis. In conclusion, our findings indicate that certain CpG-ODN induce low amounts of TNF-alpha in human B lymphocytes and may therefore be used to modulate Th2-biased immune responses in allergic patients.
Bohle
B
B
Department of Pathophysiology, Division of Immunopathology, University of Vienna, Vienna, Austria. barbara.bohle@akh-wien.ac.at
Orel
L
L
Kraft
D
D
Ebner
C
C
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000956:Antigens, Viral / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D018899:CpG Islands / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004669:Encephalitis Viruses, Tick-Borne / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000276:immunology* / Q000494:pharmacology; D013745:Tetanus Toxoid / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism*; D014373:Tuberculin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000502:physiology; D014765:Viral Vaccines / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; C408982:CPG-oligonucleotide; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009838:Oligodeoxyribonucleotides; D013745:Tetanus Toxoid; D014373:Tuberculin; D014409:Tumor Necrosis Factor-alpha; D014765:Viral Vaccines; D007371:Interferon-gamma