Mature dendritic cells differentiated in the presence of interferon-b and interleukin-3 prime functional antigen-specific CD8+ T cells.

Dendritic cell (DC)-based immunization represents a promising approach for the immunotherapy of cancer. The optimal conditions required to prepare DCs remain to be defined. Monocytes incubated in the presence of interferon (IFN)-β and interleukin (IL)-3 give rise to a distinct type of DCs (IFN-β/IL-3 DCs) that are particularly efficient at eliciting IFN-γ and IL-5 production by allogeneic helper T cells. We assessed the capacity of this new type of DCs to prime antigen-specific naive CD8⁺ T cells and compared them to the conventional DCs differentiated in the presence of granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-4 (GM-CSF/IL-4 DCs). We demonstrate that IFN-β/IL-3 DCs matured by TLR3 or CD40 ligation efficiently prime Melan-A₂₆₋₃₅-specific CD8⁺ T cellsin vitro, at a similar level as GM-CSF/IL-4 DCs. Activated antigen-specific CD8⁺ T cells produced IFN-γ and displayed potent cytotoxic activity against peptide-pulsed target cells. Expansion of CD8⁺ T cell numbers was generally higher following priming with CD40-L than with polyinosinic–polycytidylic acid (poly I:C) matured DCs. Cytolytic activity was induced by both maturing agents. These data indicate that IFN-β/IL-3 DCs represent a promising cell population for the immunotherapy of cancer. [ABSTRACT FROM AUTHOR]