Linked Life Data

20187300

Source:http://linkedlifedata.com/resource/pubmed/id/20187300

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8B
pubmed:dateCreated
2010-2-25
pubmed:abstractText
Inflammation triggered by microbial lipopolysaccharide (LPS) through Toll-like receptor (TLR) 4 in the presence of interferon (IFN)-gamma induces cytokine secretion in dendritic cells (DCs) tightly regulated by a defined differentiation program. This DC differentiation is characterized not only by a dynamic immune activating but also by tolerance-inducing phenotype associated with down-modulation of cytokines previously considered to be irreversible. CD40L on activated T cells further modifies DC differentiation. Using DNA micro-arrays, we showed down-regulated mRNA levels of TLR signalling molecules, whereas CD40/CD40L signalling molecules were up-regulated at a time when LPS/IFN-gamma-activated DCs had ceased cytokine expression. Accordingly, we demonstrated that CD40/CD40L but not TLR4 or TLR3 signalling mediated by LPS or poly (cytidylic-inosinic) acid (poly I:C) and dsRNA re-established the capacity for secreting interleukin (IL)-12 in primarily LPS/IFN-gamma-activated DCs, which have exhausted their potential for cytokine secretion. The resulting TH1 polarizing DC phenotype - which lacked accompanying secretion of the crucial immune suppressive factor IL-10 - maintained the potential for activation of cytotoxic T lymphocytes (CTLs). We therefore conclude that immune modulation is restricted to a secondary T-cell-mediated stimulus at an exhausted DC state, which prevents an immune tolerant DC phenotype. These findings impact on the rational design of TLR-activated DC-based cancer vaccines for the induction of anti-tumoural CTL responses.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1582-4934
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1741-50
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
CD40 ligation restores type 1 polarizing capacity in TLR4-activated dendritic cells that have ceased interleukin-12 expression.
pubmed:affiliation
Laboratory of Tumor Immunology, St. Anna Children's Cancer Research Institute, Vienna, Austria.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't