Oligodeoxynucleotides containing CpG motifs induce low levels of TNF-alphain human B lymphocytes: Possible adjuvants for Th1 responses

Oligodeoxynucleotides containing CpG motifs (CpG-ODN) represent potential a djuvants for specific immunotherapy of type I allergies because they foster Th1-like immune responses. However, previous work has shown that CpG-ODN i nduce systemically active levels of TNF-alpha in murine macrophages. The go al of the present study was to evaluate the release of TNF-alpha in human c ells by a CpG-ODN proven to induce Th1 immune responses in cells from atopi c individuals and in mice. CpG-ODN induced TNF-alpha in cells from atopic a nd healthy individuals. However, the amounts were low, as determined by com parison with commonly used Ags, Intracellular cytokine staining of PBMC rev ealed that CpG-ODN-induced TNF-alpha derived exclusively from B lymphocytes . TNF-cu contributed to the CpG-ODN-augmented proliferation and Tg synthesi s 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 h uman B lymphocytes and may therefore be used to modulate Th2-biased immune responses in allergic patients.