The aorta can act as site of naïve CD4+ T cell priming

MacRitchie, N. et al. (2019) The aorta can act as site of naïve CD4+ T cell priming. Cardiovascular Research, (doi:10.1093/cvr/cvz102) (PMID:30980670) (Early Online Publication)

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Abstract

Aims: Aortic adaptive immunity plays a role in atherosclerosis; however, the precise mechanisms leading to T-cell activation in the arterial wall remain poorly understood. Methods and results: Here, we have identified naïve T cells in the aorta of wild-type and T-cell receptor transgenic mice and we demonstrate that naïve T cells can be primed directly in the vessel wall with both kinetics and frequency of T-cell activation found to be similar to splenic and lymphoid T cells. Aortic homing of naïve T cells is regulated at least in part by the P-selectin glycosylated ligand-1 receptor. In experimental atherosclerosis the aorta supports CD4+ T-cell activation selectively driving Th1 polarization. By contrast, secondary lymphoid organs display Treg expansion. Conclusion: Our results demonstrate that the aorta can support T-cell priming and that naïve T cells traffic between the circulation and vessel wall. These data underpin the paradigm that local priming of T cells specific for plaque antigens contributes to atherosclerosis progression.

Item Type:Articles
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Garside, Professor Paul and MacRitchie, Dr Neil and Guzik, Professor Tomasz and Noonan, Dr Jonathan and Benson, Dr Robert and Maffia, Dr Pasquale and Schroeder, Dr Juliane and Grassia, Dr Gianluca and Hughes, Dr Catherine
Authors: MacRitchie, N., Grassia, G., Noonan, J., Cole, J. E., Hughes, C. E., Schroeder, J., Benson, R. A., Cochain, C., Zernecke, A., Guzik, T. J., Garside, P., Monaco, C., and Maffia, P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Cardiovascular Research
Publisher:Oxford University Press
ISSN:0008-6363
ISSN (Online):1755-3245
Published Online:13 April 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Cardiovascular Research 2019
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
614711Defining innate and adaptive immune functions of plasmacytoid dendritic cells in atherosclerosis.Pasquale MaffiaBritish Heart Foundation (BHF)PG/12/81/29897III -IMMUNOLOGY
617771BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177RI CARDIOVASCULAR & MEDICAL SCIENCES
644661In Situ Nanoparticle Assemblies for Healthcare Diagnostics and TherapyPasquale MaffiaEngineering and Physical Sciences Research Council (EPSRC)EP/L014165/1III -IMMUNOLOGY
682541NanoMATePasquale MaffiaEuropean Commission (EC)661369III -IMMUNOLOGY

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