| Autor: |
Boullart AC; Department of Tumor Immunology, Nijmegen Centre for Molecular Life Science, Radboud University Nijmegen Medical Centre, P.O.Box 9101, 6500 HB Nijmegen, The Netherlands., Aarntzen EH, Verdijk P, Jacobs JF, Schuurhuis DH, Benitez-Ribas D, Schreibelt G, van de Rakt MW, Scharenborg NM, de Boer A, Kramer M, Figdor CG, Punt CJ, Adema GJ, de Vries IJ |
| Jazyk: |
angličtina |
| Zdroj: |
Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2008 Nov; Vol. 57 (11), pp. 1589-97. Date of Electronic Publication: 2008 Mar 06. |
| DOI: |
10.1007/s00262-008-0489-2 |
| Abstrakt: |
Dendritic cells (DC) are professional antigen-presenting cells of the immune system that play a key role in regulating T cell-based immunity. In vivo, the capacity of DC to activate T cells depends on their ability to migrate to the T cell areas of lymph nodes as well as on their maturation state. Depending on their cytokine-secreting profile, DC are able to skew the immune response in a specific direction. In particular, IL-12p70 producing DC drive T cells towards a T helper 1 type response. A serious disadvantage of current clinical grade ex vivo generated monocyte-derived DC is the poor IL-12p70 production. We have investigated the effects of Toll-like receptor (TLR)-mediated maturation on ex vivo generated human monocyte-derived DC. We demonstrate that in contrast to cytokine-matured DC, DC matured with poly(I:C) (TLR3 ligand) and/or R848 (TLR7/8 ligand) are able to produce vast amounts of IL-12p70, but exhibit a reduced migratory capacity. The addition of prostaglandin E2 (PGE2) improved the migratory capacity of TLR-ligand matured DC while maintaining their IL-12p70 production upon T cell encounter. We propose a novel clinical grade maturation protocol in which TLR ligands poly(I:C) and R848 are combined with PGE2 to generate DC with both high migratory capacity and IL-12p70 production upon T cell encounter. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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