Adjuvant effects of CpG oligodeoxynucleotides on responses against T-independent type 2 antigens

Oligodeoxynucleotides containing CpG motifs (CpG-ODN) are potent in vitro B -cell activators and they have been successfully used to increase in vivo a ntibody responses to T-dependent peptide and protein antigens. In contrast. the use of CpG-ODN to enhance in vivo antibody responses to various T-inde pendent type 2 (TI-2) antigens has recently generated contradictory results . In this study, we compared the CpG-ODN stimulatory effect on antibody res ponses of adult and young BALB/c mice to trinitrophenylaminoethyl-carboxyme thyl (TNP) -Ficoll and to polysaccharides (PS) from several distinct seroty pes of Streptococcus pneumoniae (SPn). CpG-ODN co-administration significan tly enhanced antigen-specific immunoglobulin M (IgM), IgG, IgG1 and IgG2a t itres to TNP-Ficoll. The depletion of CD4(+) cells by monclonal antibodies (GK1.5) identified their essential role in CpG-ODN-mediated enhancement of antibody responses. In contrast to TNP-Ficoll, CpG-ODN failed to enhance Ig M and IgG responses to any of the 18 SPnPS serotypes tested. Providing T-ce ll epitopes by the conjugation of SPnPS to the carrier protein tetanus toxo id again allowed CpG-ODN to mediate enhancement of IgG, IgG2a and IgG3 resp onses to most SPnPS serotypes. Thus, antigen-presenting cell/T-cell interac tion appears to largely mediate the in vivo influence of CpG-ODN on antibod y responses to TI-2 antigens. In early life, additional factors limit CpG-O DN modulation of antibody responses to TI-2 antigens.