Tl. Warren et al., APC stimulated by CpG oligodeoxynucleotide enhance activation of MHC classI-restricted T cells, J IMMUNOL, 165(11), 2000, pp. 6244-6251
Oligonucleotides containing unmethylated CpG motifs (cytosine-phosphorothio
ate-guanine oligodeoxynucleotide (CpG ODN)) are potent immunostimulatory ag
ents 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 vitr
o, CpG ODN had no direct effect on highly purified T cells. In vitro, CpG O
DN 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 obvia
te the role of T cell help. The enhanced ability of CpG ODN-treated DCs to
activate T cells was present but blunted when Des derived from IL-12 knocko
ut 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 i
mmune response by stimulating APCs such as DCs, to produce IL-12 and other
soluble factors.