Linked Life Data

16301646

Source:http://linkedlifedata.com/resource/pubmed/id/16301646

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2005-11-22
pubmed:abstractText
Adaptation of the T cell activation threshold may be one mechanism to control autoreactivity. To investigate its occurrence in vivo, we engineered a transgenic mouse model with increased TCR-dependent excitability by expressing a Zap70 gain-of-function mutant (ZAP-YEEI) in postselection CD8 thymocytes and T cells. Increased basal phosphorylation of the Zap70 substrate linker for activation of T cells was detected in ZAP-YEEI-bearing CD8 T cells. However, these cells were not activated, but had reduced levels of TCR and CD5. Moreover, they produced lower cytokine amounts and showed faster dephosphorylation of linker for activation of T cells and ERK upon activation. Normal TCR levels and cytokine production were restored by culturing cells in the absence of TCR/spMHC interaction, demonstrating dynamic tuning of peripheral T cell responses. The effect of avidity for self-ligand(s) on this sensory adaptation was studied by expressing ZAP-YEEI in P14 or HY TCR transgenic backgrounds. Unexpectedly, double-transgenic animals expressed ZAP-YEEI prematurely in double-positive thymocytes, but no overt alteration of selection processes was observed. Instead, modifications of TCR and CD5 expression due to ZAP-YEEI suggested that signal tuning occurred during thymic maturation. Importantly, although P14 x ZAP-YEEI peripheral CD8 T cells were reduced in number and showed lower Ag-induced cytokine production and limited lymphopenia-driven proliferation, the peripheral survival/expansion and Ag responsiveness of HY x ZAP-YEEI cells were enhanced. Our data provide support for central and peripheral sensory T cell adaptation induced as a function of TCR avidity for self-ligands and signaling level. This may contribute to buffer excessive autoreactivity while optimizing TCR repertoire usage.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
175
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7388-97
pubmed:dateRevised
2011-4-6
pubmed:meshHeading
pubmed-meshheading:16301646-Adoptive Transfer, pubmed-meshheading:16301646-Animals, pubmed-meshheading:16301646-Antigens, CD5, pubmed-meshheading:16301646-Autoantigens, pubmed-meshheading:16301646-CD8-Positive T-Lymphocytes, pubmed-meshheading:16301646-Clonal Deletion, pubmed-meshheading:16301646-Cytokines, pubmed-meshheading:16301646-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:16301646-Flow Cytometry, pubmed-meshheading:16301646-H-Y Antigen, pubmed-meshheading:16301646-Immune Tolerance, pubmed-meshheading:16301646-Immunoblotting, pubmed-meshheading:16301646-Immunoprecipitation, pubmed-meshheading:16301646-Lymphocyte Activation, pubmed-meshheading:16301646-Major Histocompatibility Complex, pubmed-meshheading:16301646-Mice, pubmed-meshheading:16301646-Mice, Inbred C57BL, pubmed-meshheading:16301646-Mice, Transgenic, pubmed-meshheading:16301646-Phosphorylation, pubmed-meshheading:16301646-Receptors, Antigen, T-Cell, pubmed-meshheading:16301646-Thymus Gland, pubmed-meshheading:16301646-ZAP-70 Protein-Tyrosine Kinase
pubmed:year
2005
pubmed:articleTitle
CD8 T cell sensory adaptation dependent on TCR avidity for self-antigens.
pubmed:affiliation
Molecular Immunology Unit, Department of Immunology, Institut Pasteur, Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't