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

Abstract

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 cells in 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.