Mature dendritic cells differentiated in the presence of interferon-beta 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)-beta and interleukin (IL)-3 give rise to a distinct type of DCs (IFN-beta/IL-3 DCs) that are particularly efficient at eliciting IFN-gamma 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-beta/IL-3 DCs matured by TLR3 or CD40 ligation efficiently prime Melan-A(26-35)-specific CD8(+) T cells in vitro, at a similar level as GM-CSF/IL-4 DCs. Activated antigen-specific CD8(+) T cells produced IFN-gamma 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-beta/IL-3 DCs represent a promising cell population for the immunotherapy of cancer.
Renneson
J
J
Cancer Research Tumour Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
Salio
M
M
Mazouz
N
N
Goldman
M
M
Marchant
A
A
Cerundolo
V
V
D023201:CD40 Ligand / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D016899:Interferon-beta / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D007377:Interleukin-3 / Q000276:immunology*; D015848:Interleukin-5 / Q000276:immunology; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000276:immunology / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D019496:Cancer Vaccines; D007377:Interleukin-3; D015848:Interleukin-5; D023201:CD40 Ligand; D016899:Interferon-beta; D007371:Interferon-gamma
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