Linked Life Data

18021470

Source:http://linkedlifedata.com/resource/pubmed/id/18021470

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2007-11-20
pubmed:abstractText
Advanced cutaneous T-cell lymphoma (CTCL) is typically associated with a variety of profound defects of cellular immunity, including depressed dendritic cell numbers and function. Therefore, we investigated the ability of synthetic imidazoquinolines, which are agonists for Toll-like receptors (TLRs) 7 and 8, to enhance in vitro the cell-mediated immunity of patients with leukemic CTCL and Sézary syndrome. Patients' peripheral blood mononuclear cells (PBMCs) stimulated with the TLR7 agonist 3M-001 produced high levels of interferon (IFN)-alpha, and the TLR8 agonist 3M-002 potently induced predominantly interleukin (IL)-12 and IFN-gamma. Marked upregulation of CD69 and CD25 on natural killer (NK) cells and T cells from patients and an increase in NK cytolytic activity was also observed. We further demonstrate that priming of patients' PBMCs with IFN-gamma has the ability to synergistically enhance the production of IL-12 induced by a synthetic agonist for TLR8. The underlying mechanisms of increased IL-12 production in response to priming with IFN appears to involve an increase in IL-12 p35 and IL-12 p40 gene transcription and a decrease in IL-10 levels upon stimulation with the TLR8 agonist. Our data demonstrate the ability of imidazoquinolines to potently stimulate cellular immune responses of patients with CTCL and emphasizes the benefit of using a combination of biologic modifiers to further enhance their immune responses.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1557-9190
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
524-34
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Synthetic imidazoquinolines potently and broadly activate the cellular immune response of patients with cutaneous T-cell lymphoma: synergy with interferon-gamma enhances production of interleukin-12.
pubmed:affiliation
Department of Dermatology, University of Pennsylvania, PA 19104, USA. mwysocka@mail.med.upenn.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural