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- Title
Combination of monocyte-derived dendritic cells and activated T cells which express CD40 ligand: a new approach to cancer immunotherapy.
- Authors
Takami Sato; Mizue Terai; Rie Yasuda; Ryuko Watanabe; Berd, David; Mastrangelo, Michael J.; Kenichiro Hasumi
- Abstract
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 γ (IFN-γ). 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-β (MIP-3β). ATs also migrated toward the MIP-3β. These results suggest a combination of DCs and ATs as a potentially effective therapeutic strategy.
- Subjects
DENDRITIC cells; LYMPHOCYTES; CELL communication; VACCINATION; GRANULOCYTE-macrophage colony-stimulating factor; T cells
- Publication
Cancer Immunology, Immunotherapy, 2004, Vol 53, Issue 1, p53
- ISSN
0340-7004
- Publication type
Article
- DOI
10.1007/s00262-003-0419-2