Enhancement of antigen-presenting cell surface molecules involved in cognate interactions by immunostimulatory DNA sequences

Bacterial genomic DNA, plasmid DNA (pDNA) and synthetic oligodeoxynucleotid es (ODN) containing immunostimulatory DNA sequences (ISS) have been propose d to foster a T(h)1 response via the release of type 1 cytokines from macro phages, dendritic cells, NK cells and B cells, In this study, we show that ISS-enriched DNA up-regulates a distinct profile of cell surface molecules on macrophages and B cells in vitro and in vivo. ISS-ODN and ISS-containing pDNA enhanced the expression of antigen presentation molecules (MHC class I and II), co-stimulatory molecules (B7-1, B7-2 and CD40), cytokine recepto rs (IFN-gamma receptor and IL-2 receptor), an adhesion molecule (ICAM-1) an d an Fc receptor (Fc gamma receptor) on murine B cells or bone marrow-deriv ed macrophages, The increased expression of these surface molecules is seen in purified cell populations and is largely independent of the effects of type 1 cytokines, Splenic antigen-presenting cells stimulated with ISS-ODN in vivo efficiently activate naive T cells and bias their differentiation t oward a T(h)1 phenotype in vitro, Thus, the induction of both type 1 cytoki nes and a distinct profile of cell surface molecules contributes to the pot ent immunostimulatory effects of ISS-containing DNA on innate and adaptive immunity.