Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1998-12-7
pubmed:abstractText
CD4+ memory T cells coordinate immune responses against viruses and other pathogens via the Ag-induced secretion of potent effector cytokines. The efficacy of these responses depends on both the overall number of pathogen-specific memory T cells and the particular array of cytokines that these cells are programmed to secrete. Here, we provide evidence that heterogeneity in Ag triggering thresholds constitutes an additional critical determinant of memory T cell function. Using a novel assay that allows single-cell detection of Ag-specific T cell cytokine production, we demonstrate that CMV-specific CD4+ memory cells from human peripheral blood display pronounced differences in their costimulatory requirements for Ag-induced triggering of IFN-gamma and IL-2 secretion, ranging from cells that trigger with little costimulation (e.g., resting APC alone) to cells requiring potent costimulation through multiple pathways (resting APC plus multiple costimulatory mAbs, or activated APC). These differences in costimulatory requirements are independent of clonal differences in TCR signaling intensity, consistent with an intrinsic activation-threshold heterogeneity that is "downstream" from the TCR. Thus, "effective" frequencies of Ag-specific CD4+ memory T cells appear to depend on the activation status of available APC, a dependence that would allow the immune system to rapidly adjust the number of functional Ag-specific memory T cells in a particular effector site according to local conditions.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
161
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5284-95
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9820501-Antibodies, Monoclonal, pubmed-meshheading:9820501-Antigen-Presenting Cells, pubmed-meshheading:9820501-Antigens, CD, pubmed-meshheading:9820501-Antigens, CD28, pubmed-meshheading:9820501-Antigens, CD5, pubmed-meshheading:9820501-CD4-Positive T-Lymphocytes, pubmed-meshheading:9820501-Cytokines, pubmed-meshheading:9820501-Cytomegalovirus, pubmed-meshheading:9820501-Epitopes, T-Lymphocyte, pubmed-meshheading:9820501-Humans, pubmed-meshheading:9820501-Immunologic Memory, pubmed-meshheading:9820501-Inflammation, pubmed-meshheading:9820501-Lectins, C-Type, pubmed-meshheading:9820501-Lymphocyte Activation, pubmed-meshheading:9820501-Lymphocyte Count, pubmed-meshheading:9820501-Membrane Glycoproteins, pubmed-meshheading:9820501-NK Cell Lectin-Like Receptor Subfamily D, pubmed-meshheading:9820501-Receptors, Antigen, T-Cell, alpha-beta, pubmed-meshheading:9820501-Signal Transduction, pubmed-meshheading:9820501-T-Lymphocyte Subsets, pubmed-meshheading:9820501-Tumor Necrosis Factor-alpha
pubmed:year
1998
pubmed:articleTitle
Normal human CD4+ memory T cells display broad heterogeneity in their activation threshold for cytokine synthesis.
pubmed:affiliation
Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't