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

MacRitchie N., Grassia G., Noonan J., Cole JE., Hughes CE., Schroeder J., Benson RA., Cochain C., Zernecke A., Guzik TJ., Garside P., Monaco C., Maffia P.

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.

DOI

10.1093/cvr/cvz102

Type

Journal article

Publication Date

2020-02-01T00:00:00+00:00

Volume

116

Pages

306 - 316

Total pages

10

Keywords

Aorta, Atherosclerosis, Priming, T cells, Adaptive Immunity, Animals, Aorta, Aortic Diseases, Atherosclerosis, Cell Proliferation, Cells, Cultured, Cytokines, Disease Models, Animal, Disease Progression, Genes, T-Cell Receptor, Kinetics, Lymphocyte Activation, Membrane Glycoproteins, Mice, Inbred C57BL, Mice, Knockout, ApoE, Phenotype, Plaque, Atherosclerotic, T-Lymphocytes, Regulatory, Th1 Cells

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