Combination of monocyte-derived dendritic cells and activated T cells which express CD40 ligand: a new approach to cancer immunotherapy.
Interactions between dendritic cells (DCs) and activated T cells are critically important for the establishment of an effective immune response. To develop the basis for a new DC-based cancer vaccine, we investigated cell-to-cell interactions between human monocyte-derived DCs and autologous T cells that are activated to express the CD40 ligand (CD40L). Peripheral blood monocytes were cultured in the presence of granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 4 (IL-4) to induce differentiation of DCs. Activated T cells (ATs) consisted of autologous peripheral blood lymphocytes that had been activated with phytohemagglutinin (PHA) and then stimulated with calcium ionophore to up-regulate expression of CD40L. Coculture of these DCs and ATs induced significant production of interleukin 12 (IL-12) and also enhanced the production of interferon gamma (IFN-gamma). The production of IL-12 was blocked by an anti-CD40L antibody or by separation of the DC and AT fractions by a permeable membrane. Furthermore, coculture of DCs and ATs induced DCs to upregulate CD83 expression and stimulated migration of DCs toward the macrophage inflammatory protein 3-beta (MIP-3beta). ATs also migrated toward the MIP-3beta. These results suggest a combination of DCs and ATs as a potentially effective therapeutic strategy.
D020533:Angiogenesis Inhibitors / Q000378:metabolism; D015703:Antigens, CD; D000970:Antineoplastic Agents / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D054415:Chemokine CCL19; D019742:Chemokines, CC / Q000378:metabolism; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000276:immunology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation; D000097802:CD83 Antigen
D020533:Angiogenesis Inhibitors; D015703:Antigens, CD; D000970:Antineoplastic Agents; D019013:CD40 Antigens; D023201:CD40 Ligand; D002118:Calcium; D054415:Chemokine CCL19; D019742:Chemokines, CC; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007136:Immunoglobulins; D007371:Interferon-gamma; D018664:Interleukin-12; D015847:Interleukin-4; D008562:Membrane Glycoproteins; D010835:Phytohemagglutinins; D000097802:CD83 Antigen; C515460:CCL19 protein, human