Development of Spontaneous Anergy in Invariant Natural Killer T Cells in a Mouse Model of Dyslipidemia
| Autor: | Hideo Yagita, Luc Van Kaer, Roman Covarrubias, Nicole A. Braun, Steven A. Porcelli, Paul B. Savage, Amy S. Major, Yanice V. Mendez-Fernandez |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
Interleukin 2 Time Factors Lymphocyte medicine.medical_treatment Programmed Cell Death 1 Receptor Receptors Antigen T-Cell Antigen-Presenting Cells Galactosylceramides Hyperlipidemias Biology Lymphocyte Activation Article Natural killer cell Mice Apolipoproteins E medicine Animals Lymphocyte Count Antigen-presenting cell Cells Cultured Cell Proliferation Clonal Anergy Mice Knockout Clonal anergy Cell growth Dendritic Cells Natural killer T cell Mice Inbred C57BL Disease Models Animal Phenotype medicine.anatomical_structure Cytokine Antigens Surface Chronic Disease Immunology Cytokines Interleukin-2 Natural Killer T-Cells Apoptosis Regulatory Proteins Cardiology and Cardiovascular Medicine Injections Intraperitoneal NK Cell Lectin-Like Receptor Subfamily A medicine.drug |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 30:1758-1765 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/atvbaha.110.206045 |
| Popis: | 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 α-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. Conclusion— 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|