Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2010-4-16
pubmed:abstractText
Natural killer (NK) cells play an important role in the immunosurveillance of leukemia. Their reactivity is governed by a balance of activating and inhibitory receptors including various members of the tumor necrosis factor receptor (TNFR) family. Here we report that human NK cells acquire expression of the TNFR family member CD137 upon activation, and NK cells of acute myeloid leukemia (AML) patients display an activated phenotype with substantial CD137 expression. CD137 ligand (CD137L) was detectable on leukemic cells in 35% of 65 investigated AML patients, but not on healthy CD34(+) cells, and expression was associated with monocytic differentiation. Bidirectional signaling following CD137-CD137L interaction induced the release of the immunomodulatory cytokines interleukin-10 and TNF by AML cells and directly diminished granule mobilization, cytotoxicity, and interferon-gamma production of human NK cells, which was restored by blocking CD137. Cocultures of NK cells with CD137L transfectants confirmed that human CD137 inhibits NK-cell reactivity, while activating signals were transduced by its counterpart on NK cells in mice. Our data underline the necessity to study the function of seemingly analog immunoregulatory molecules in mice compared with men and demonstrate that CD137-CD137L interaction enables immune evasion of AML cells by impairing NK-cell tumor surveillance in humans.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
115
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3058-69
pubmed:dateRevised
2011-1-12
pubmed:meshHeading
pubmed-meshheading:20008791-4-1BB Ligand, pubmed-meshheading:20008791-Aged, pubmed-meshheading:20008791-Aged, 80 and over, pubmed-meshheading:20008791-Animals, pubmed-meshheading:20008791-Antigens, CD137, pubmed-meshheading:20008791-Cell Line, Tumor, pubmed-meshheading:20008791-Cytokines, pubmed-meshheading:20008791-Female, pubmed-meshheading:20008791-Gene Expression Regulation, Leukemic, pubmed-meshheading:20008791-Histocompatibility Antigens Class I, pubmed-meshheading:20008791-Humans, pubmed-meshheading:20008791-Immune Tolerance, pubmed-meshheading:20008791-Killer Cells, Natural, pubmed-meshheading:20008791-Leukemia, Myeloid, Acute, pubmed-meshheading:20008791-Lymphocyte Activation, pubmed-meshheading:20008791-Male, pubmed-meshheading:20008791-Mice, pubmed-meshheading:20008791-Middle Aged, pubmed-meshheading:20008791-Protein Binding, pubmed-meshheading:20008791-Signal Transduction, pubmed-meshheading:20008791-Up-Regulation
pubmed:year
2010
pubmed:articleTitle
CD137 ligand mediates opposite effects in human and mouse NK cells and impairs NK-cell reactivity against human acute myeloid leukemia cells.
pubmed:affiliation
Department of Hematology/Oncology, Eberhard-Karls University, 72076 Tuebingen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't