Combination of monocyte-derived dendritic cells and activated T cells which express CD40 ligand: a new approach to cancer immunotherapy.

Autor: Sato T; Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA 19107, USA, t_sato@mail.jci.tju.edu, Terai M, Yasuda R, Watanabe R, Berd D, Mastrangelo MJ, Hasumi K
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2004 Jan; Vol. 53 (1), pp. 53-61. Date of Electronic Publication: 2003 Sep 10.
DOI: 10.1007/s00262-003-0419-2
Abstrakt: 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.
Databáze: MEDLINE