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Programmed Cell Death-1 Deficiency Exacerbates T Cell Activation and Atherogenesis despite Expansion of Regulatory T Cells in Atherosclerosis-Prone Mice

Please always quote using this URN: urn:nbn:de:bvb:20-opus-119823
  • T cell activation represents a double-edged sword in atherogenesis, as it promotes both pro-inflammatory T cell activation and atheroprotective Foxp3(+) regulatory T cell (Treg) responses. Here, we investigated the role of the co-inhibitory receptor programmed cell death-1 (PD-1) in T cell activation and CD4(+) T cell polarization towards pro-atherogenic or atheroprotective responses in mice. Mice deficient for both low density lipoprotein receptor and PD-1 (Ldlr(-/-)Pd1(-/-)) displayed striking increases in systemic CD4(+) and CD8(+) T cellT cell activation represents a double-edged sword in atherogenesis, as it promotes both pro-inflammatory T cell activation and atheroprotective Foxp3(+) regulatory T cell (Treg) responses. Here, we investigated the role of the co-inhibitory receptor programmed cell death-1 (PD-1) in T cell activation and CD4(+) T cell polarization towards pro-atherogenic or atheroprotective responses in mice. Mice deficient for both low density lipoprotein receptor and PD-1 (Ldlr(-/-)Pd1(-/-)) displayed striking increases in systemic CD4(+) and CD8(+) T cell activation after 9 weeks of high fat diet feeding, associated with an expansion of both pro-atherogenic IFNγ-secreting T helper 1 cells and atheroprotective Foxp3+ Tregs. Importantly, PD-1 deficiency did not affect Treg suppressive function in vitro. Notably, PD-1 deficiency exacerbated atherosclerotic lesion growth and entailed a massive infiltration of T cells in atherosclerotic lesions. In addition, aggravated hypercholesterolemia was observed in Ldlr(-/-)Pd1(-/-) mice. In conclusion, we here demonstrate that although disruption of PD-1 signaling enhances both pro- and anti-atherogenic T cell responses in Ldlr(-/-) mice, pro-inflammatory T cell activation prevails and enhances dyslipidemia, vascular inflammation and atherosclerosis.show moreshow less

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Metadaten
Author: Clement Cochain, Sweena M. Chaudhari, Miriam Koch, Heinz Wiendl, Hans-Henning Eckstein, Alma Zernecke
URN:urn:nbn:de:bvb:20-opus-119823
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Klinische Biochemie und Pathobiochemie
Language:English
Parent Title (English):PLoS ONE
ISSN:1932-6203
Year of Completion:2014
Volume:9
Issue:4
Pagenumber:e93280
Source:PLoS ONE 9(4): e93280. doi:10.1371/journal.pone.0093280
DOI:https://doi.org/10.1371/journal.pone.0093280
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=24691202
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:T cells; regulatory T cells
aorta; atherosclerosis; cytotoxic T cells; diet; nutritional deficiencies; spleen
Release Date:2015/11/17
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung