Both authors contributed equally to this work.
CD40 ligation during dendritic cell maturation reduces cell death and prevents interleukin-10-induced regression to macrophage-like monocytes
Version of Record online: 13 DEC 2007
© 2007 The Authors. Journal compilation © 2007 Blackwell Munksgaard
Volume 17, Issue 3, pages 177–187, March 2008
How to Cite
Haenssle, H., Buhl, T., Knudsen, S., Krueger, U., Rosenberger, A., Reich, K. and Neumann, C. (2008), CD40 ligation during dendritic cell maturation reduces cell death and prevents interleukin-10-induced regression to macrophage-like monocytes. Experimental Dermatology, 17: 177–187. doi: 10.1111/j.1600-0625.2007.00668.x
Conflict of interest statement: All authors declare no conflict of interest. The corresponding author has full access to all the data in the study and had final responsibility for the decision to submit the manuscript for publication.
- Issue online: 13 DEC 2007
- Version of Record online: 13 DEC 2007
- Accepted for publication 16 November 2007
- bcl-XL expression;
- cell survival;
- cytokine cocktail;
- dendritic cells;
Abstract: Dendritic cells (DCs) have become popular candidates in cancer vaccination because of their crucial role in inducing T-cell responses. However, clinical studies greatly differ in their protocols for generating DCs and the efficacy in treating established tumors needs to be improved. We systematically analyzed DCs maturated by five different protocols for surface markers, the alloproliferative T-cell response, the DC survival after cytokine deprivation, the stability of surface markers under the influence of interleukin-10 (IL-10) and the DC cytokine secretion pattern. Monocyte-derived DCs were maturated by CD40-ligand (CD40-L), unmethylated cytosine–guanosine dinucleotides-oligodinucleotides (CpG-ODN), an inflammatory cytokine cocktail (ICC), a combination of ICC and CD40-L, or ICC, CD40-L and CpG-ODN. A high co-expression of DC maturation and costimulation markers was found after treatment with ICC plus CD40-L (69.3 ± 9.6% CD83/CD80 double positive staining) and correlated with a significantly increased cell survival, a high expression of the antiapoptotic factor bcl-XL, a stable CD83high/CD14low expression under the influence of IL-10, and a strong alloproliferative T-cell response. In conclusion, our data support the use of maturation protocols containing ICC plus CD40-L in order to generate highly mature, phenotypically stable, cell-death resistant, and T-cell stimulatory DCs for clinical application in cancer patients.