Epitopes described in "Development of spontaneous anergy in invariant natural killer T cells in a mouse model of dyslipidemia."

Article Authors:Nicole A Braun; Yanice V Mendez-Fernandez; Roman Covarrubias; Steven A Porcelli; Paul B Savage; Hideo Yagita; Luc Van Kaer; Amy S Major
Article Title:Development of spontaneous anergy in invariant natural killer T cells in a mouse model of dyslipidemia.
Reference Detail
Reference ID:1026229
Abstract:OBJECTIVE: In this study, we investigated whether dyslipidemia-associated perturbed invariant natural killer T (iNKT) cell function is due to intrinsic changes in iNKT cells or defects in the ability of antigen-presenting cells to activate iNKT cells. METHODS AND RESULTS: We compared iNKT cell expansion and cytokine production in C57BL/6J (B6) and apolipoprotein E-deficient (apoE(-/-)) mice. In response to in vivo stimulation with alpha-galactosylceramide, a prototypic iNKT cell glycolipid antigen, apoE(-/-) mice showed significantly decreased splenic iNKT cell expansion at 3 days after injection, a profile associated with iNKT cell anergy due to chronic stimulation. This decrease in expansion and cytokine production was accompanied by a 2-fold increase in percentage of iNKT cells expressing the inhibitory marker programmed death-1 in apoE(-/-) mice compared with controls. However, in vivo and in vitro blockade of programmed death-1 using monoclonal antibody was not able to restore functions of iNKT cells from apoE(-/-) mice to B6 levels. iNKT cells from apoE(-/-) mice also had increased intracellular T cell receptor and Ly49 expression, a phenotype associated with previous activation. Changes in iNKT cell functions were cell autonomous, because dendritic cells from apoE(-/-) mice were able to activate B6 iNKT cells, but iNKT cells from apoE(-/-) mice were not able to respond to B6 dendritic cells. CONCLUSIONS: These data suggest that chronic dyslipidemia induces an iNKT cell phenotype that is unresponsive to further simulation by exogenous glycolipid and that sustained unresponsiveness is iNKT cell intrinsic.
Affiliations:Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Reference Type:Literature
PubMed ID:20539017
Journal:Arterioscler Thromb Vasc Biol
Journal Volume:30
Article Pages:1758-65
Journal ISSN:1524-4636
Article Chemical List:Antigens, Surface;Apolipoproteins E;Apoptosis Regulatory Proteins;Cytokines;Galactosylceramides;Interleukin-2;NK Cell Lectin-Like Receptor Subfamily A;Pdcd1 protein, mouse;Programmed Cell Death 1 Receptor;Receptors, Antigen, T-Cell;alpha-galactosylceramide
Article MeSH List:Animals; Antigen-Presenting Cells(immunology); Antigens, Surface(metabolism); Apolipoproteins E(deficiency; genetics); Apoptosis Regulatory Proteins(metabolism); Cell Proliferation; Cells, Cultured; Chronic Disease; Clonal Anergy; Cytokines(metabolism); Dendritic Cells(immunology); Disease Models, Animal; Galactosylceramides(administration & dosage); Hyperlipidemias(genetics; immunology); Injections, Intraperitoneal; Interleukin-2(metabolism); Lymphocyte Activation(drug effects); Lymphocyte Count; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; NK Cell Lectin-Like Receptor Subfamily A(metabolism); Natural Killer T-Cells(drug effects; immunology); Phenotype; Programmed Cell Death 1 Receptor; Receptors, Antigen, T-Cell(metabolism); Time Factors
Curation Last Updated:2016-05-11 20:12:01