PMID- 22962607
OWN - NLM
STAT- MEDLINE
DCOM- 20130122
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 9
DP  - 2012
TI  - CD86 and IL-12p70 are key players for T helper 1 polarization and natural killer 
      cell activation by Toll-like receptor-induced dendritic cells.
PG  - e44266
LID - 10.1371/journal.pone.0044266 [doi]
LID - e44266
AB  - BACKGROUND: Dendritic cells (DCs) determine the activation and polarization of T 
      cells via expression of costimulatory molecules and secretion of cytokines. The 
      function of DCs derived from monocytes ex vivo strongly depends on the 
      composition of the maturation cocktail used. METHODOLOGY/PRINCIPAL FINDINGS: We 
      analyzed the effect of costimulatory molecule expression and cytokine secretion 
      by DCs on T and natural killer (NK) cell activation by conducting a head-to-head 
      comparison of a Toll-like receptor (TLR) agonist-based cocktail with the standard 
      combination of proinflammatory cytokines or IL-10 alone. We could show that 
      TLR-induced DCs are characterized by a predominance of costimulatory over 
      coinhibitory molecules and by high secretion of IL-12p70, but not IL-10. 
      Functionally, these signals translated into an increase in IFN-gamma secreting Th1 
      cells and a decrease in regulatory T cells. T cell activation and polarization 
      were dependent on IL-12p70 and CD86, but remarkably not on CD80 signaling. By 
      means of IL-12p70 secretion, only TLR-induced DCs activated NK cells. 
      CONCLUSIONS/SIGNIFICANCE: TLR-matured DCs are highly suitable for application in 
      immunotherapeutic strategies that rely on strong type 1 polarization and NK cell 
      activation. Their effects particularly depend on high CD86 expression and 
      IL-12p70 secretion.
FAU - Lichtenegger, Felix S
AU  - Lichtenegger FS
AD  - Department of Internal Medicine III, Klinikum der Universitat Munchen, Munich, 
      Germany. Felix.Lichtenegger@med.uni-muenchen.de
FAU - Mueller, Katharina
AU  - Mueller K
FAU - Otte, Bettina
AU  - Otte B
FAU - Beck, Barbara
AU  - Beck B
FAU - Hiddemann, Wolfgang
AU  - Hiddemann W
FAU - Schendel, Dolores J
AU  - Schendel DJ
FAU - Subklewe, Marion
AU  - Subklewe M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120904
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (B7-2 Antigen)
RN  - 0 (TLR3 protein, human)
RN  - 0 (Toll-Like Receptor 3)
RN  - 130068-27-8 (Interleukin-10)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - B7-2 Antigen/genetics/*immunology
MH  - Cell Differentiation/genetics/immunology
MH  - Cell Line
MH  - Coculture Techniques
MH  - Dendritic Cells/*immunology/metabolism
MH  - Fibroblasts/metabolism
MH  - Flow Cytometry
MH  - Gene Expression/immunology
MH  - Humans
MH  - Interferon-gamma/immunology/metabolism
MH  - Interleukin-10/immunology
MH  - Interleukin-12/*immunology/metabolism
MH  - Killer Cells, Natural/*immunology/metabolism
MH  - Lymphocyte Activation/immunology
MH  - Mice
MH  - Primary Cell Culture
MH  - Signal Transduction/immunology
MH  - T-Lymphocytes, Regulatory/immunology/metabolism
MH  - Th1 Cells/*immunology/metabolism
MH  - Toll-Like Receptor 3/genetics/*immunology
PMC - PMC3433478
COIS- Competing Interests: Dolores J. Schendel declares a competing interest through 
      pending patents submitted by the Helmholtz Zentrum Munchen, German Research 
      Center for Environmental Health (Munich, Germany). These pending patents relate 
      to "Composition for the Preparation of Mature Dendritic Cells". This does not 
      alter the authors' adherence to all the PLoS ONE policies on sharing data and 
      materials.
EDAT- 2012/09/11 06:00
MHDA- 2013/01/23 06:00
PMCR- 2012/09/04
CRDT- 2012/09/11 06:00
PHST- 2012/05/10 00:00 [received]
PHST- 2012/07/31 00:00 [accepted]
PHST- 2012/09/11 06:00 [entrez]
PHST- 2012/09/11 06:00 [pubmed]
PHST- 2013/01/23 06:00 [medline]
PHST- 2012/09/04 00:00 [pmc-release]
AID - PONE-D-12-13499 [pii]
AID - 10.1371/journal.pone.0044266 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(9):e44266. doi: 10.1371/journal.pone.0044266. Epub 2012 Sep 4.