Polyriboinosinic polyribocytidylic acid (poly(I : C)) induces stable maturation of functionally active human dendritic cells

For vaccination strategies and adoptive immunotherapy purposes; immature de ndritic cells (DC) can be generated from adherent monocytes using GM-CSF an d IL-4, Presently, the only clinically applicable method to induce stable m aturation of DC is the use of supernatants of activated monocytes (monocyte -conditioned medium (MCM)), MCM contains an undefined mixture of cytokines and is difficult to standardize. Here we report that stable maturation of D C can be simply induced by the addition of polyriboinosinic polyribocytidyl ic acid (poly(I:C)), a synthetic dsRNA clinically applied as an immunomodul ator, Poly(I:C)treated DC show a mature phenotype with high expression leve ls of HLA-DR, CD86, and the DC maturation marker CD83, This mature phenotyp e is retained for 48 h after cytokine withdrawal. In contrast to untreated DC; poly(I:C)-treated DC down-regulate pinocytosis, produce high levels of IL-12 and low levels of IL-10, induce strong T cell proliferation in a prim ary allo MLR, and effectively present peptide Ags to HLA class I-restricted CTL, In conclusion, we present a simple methodology for the preparation of clinically applicable mature DC.