Human dendritic cells require multiple activation signals for the efficient generation of tumor antigen-specific T lymphocytes - PubMed (original) (raw)
Human dendritic cells require multiple activation signals for the efficient generation of tumor antigen-specific T lymphocytes
R Lapointe et al. Eur J Immunol. 2000 Nov.
Free article
Abstract
Dendritic cells (DC) are specialized cells of the immune system responsible for the initiation and regulation of both cellular and humoral responses. DC function is highly dependent on their level of maturation. In this study, we postulated that full DC maturation would require a combination of activating signals. When cultured monocyte-derived DC received stimulation with CD40 ligand (CD40L) and lipopolysaccharide (LPS) together, the IL-12 secretion increased 5-60-fold and the IL-10 secretion increased 5-15-fold when compared with either stimulation alone. In addition, poly I.C, a double-stranded RNA analog that mimics viral infection, also synergized with CD40L to stimulate DC to secrete high levels of IL-12 and IL-10. Flow cytometry revealed an up-regulation in the expression of CD80, CD86 and CD83 following activation with a soluble trimeric form of CD40L (CD40Ls) or LPS. However, no further up-regulation was observed when both CD40Ls and LPS were used together compared with a single stimulatory signal, suggesting that there was no correlation between the expression of these markers and the level of IL-12/IL-10 secretion. Finally, specific cytotoxic T lymphocytes (CTL) were generated using DC pulsed with a modified HLA-A2-restricted peptide epitope derived from the melanoma antigen MART-1. DC activated with a combination of CD40Ls and LPS were more efficient in eliciting MART-specific reactivity compared to DC activated with CD40Ls or LPS alone. These results demonstrate that multiple maturational signals have a positive impact on the ability of DC to secrete IL-12 and IL-10 and more importantly, to generate antigen-specific T lymphocytes.
Similar articles
- Sequential delivery of maturation stimuli increases human dendritic cell IL-12 production and enhances tumor antigen-specific immunogenicity.
Kalady MF, Onaitis MW, Emani S, Abdel-Wahab Z, Tyler DS, Pruitt SK. Kalady MF, et al. J Surg Res. 2004 Jan;116(1):24-31. doi: 10.1016/j.jss.2003.09.003. J Surg Res. 2004. PMID: 14732346 - The role of CD40 and CD154/CD40L in dendritic cells.
Ma DY, Clark EA. Ma DY, et al. Semin Immunol. 2009 Oct;21(5):265-72. doi: 10.1016/j.smim.2009.05.010. Epub 2009 Jun 12. Semin Immunol. 2009. PMID: 19524453 Free PMC article. Review. - CD40 and dendritic cell function.
O'Sullivan B, Thomas R. O'Sullivan B, et al. Crit Rev Immunol. 2003;23(1-2):83-107. doi: 10.1615/critrevimmunol.v23.i12.50. Crit Rev Immunol. 2003. PMID: 12906261 Review.
Cited by
- Mobilization of dendritic cell precursors in patients with cancer by flt3 ligand allows the generation of higher yields of cultured dendritic cells.
Marroquin CE, Westwood JA, Lapointe R, Mixon A, Wunderlich JR, Caron D, Rosenberg SA, Hwu P. Marroquin CE, et al. J Immunother. 2002 May-Jun;25(3):278-88. doi: 10.1097/01.CJI.0000016307.48397.27. J Immunother. 2002. PMID: 12000870 Free PMC article. - Activation of tonsil dendritic cells with immuno-adjuvants.
Polak ME, Borthwick NJ, Gabriel FG, Jager MJ, Cree IA. Polak ME, et al. BMC Immunol. 2008 Mar 18;9:10. doi: 10.1186/1471-2172-9-10. BMC Immunol. 2008. PMID: 18366670 Free PMC article. - Effects of glioma cells on maturation of dendritic cells.
Kikuchi T, Abe T, Ohno T. Kikuchi T, et al. J Neurooncol. 2002 Jun;58(2):125-30. doi: 10.1023/a:1016009528258. J Neurooncol. 2002. PMID: 12164683 - Immunomodulatory capacity of the serotonin receptor 5-HT2B in a subset of human dendritic cells.
Szabo A, Gogolak P, Koncz G, Foldvari Z, Pazmandi K, Miltner N, Poliska S, Bacsi A, Djurovic S, Rajnavolgyi E. Szabo A, et al. Sci Rep. 2018 Jan 29;8(1):1765. doi: 10.1038/s41598-018-20173-y. Sci Rep. 2018. PMID: 29379077 Free PMC article. - A composite MyD88/CD40 switch synergistically activates mouse and human dendritic cells for enhanced antitumor efficacy.
Narayanan P, Lapteva N, Seethammagari M, Levitt JM, Slawin KM, Spencer DM. Narayanan P, et al. J Clin Invest. 2011 Apr;121(4):1524-34. doi: 10.1172/JCI44327. Epub 2011 Mar 7. J Clin Invest. 2011. PMID: 21383499 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials