CpG-DNA-mediated transient lymphadenopathy is associated with a state of Th1 predisposition to antigen-driven responses

Infections can influence concurrent and subsequent Th1 vs Th2 immune respon ses to Ags, Through pattern recognition of foreign unmethylated CpG dinucle otides, the vertebrate innate immune system can sense infectious danger and typically replies with a Th1-polarized adaptive immune response. We examin ed whether CpG-DNA exposure would influence subsequent responses to infecti on and soluble Ags, CpG-DNA injection led to local lymphadenopathy characte rized by maintenance of cellular composition with some biasing toward eleva ted dendritic cell composition. Sustained local production of IL-12 and IFN -gamma from dendritic cells and T cells was shown. Prior injection by up to 2 wk with CpG-DNA protected BALB/c mice from Th2 driven lethal leishmanias is, CpG-DNA injection by up to 5 wk before soluble Ag challenge resulted in the generation of Ag-specific CTL, Th1 recall responses to Ag, and Th1-pol arized Ag-specific Abs, Thus, CpG-DNA instigated a local predisposition for intense CTL responses and Th1-polarized immune responses to subsequent inf ections or Ag challenge. The induction by the innate immune system of a loc ally contained hypersensitivity could represent a capacitating immune react ion yielding rapid conditioned responses to secondary infections.