Cardiovascular research · 2020
The aorta can act as a site of naïve CD4+ T-cell priming.
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MacRitchie Neil, Grassia Gianluca, Noonan Jonathan, Cole Jennifer E, Hughes Catherine E, Schroeder Juliane, Benson Robert A, Cochain Clement, Zernecke Alma, Guzik Tomasz J, Garside Paul, Monaco Claudia, Maffia Pasquale
Аннотация
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.
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.
Предметные рубрики MeSH
Adaptive ImmunityAnimalsAortaAortic DiseasesAtherosclerosisCell ProliferationCells, CulturedCytokinesDisease Models, AnimalDisease ProgressionGenes, T-Cell ReceptorKineticsLymphocyte ActivationMembrane GlycoproteinsMice, Inbred C57BLMice, Knockout, ApoEPhenotypePlaque, AtheroscleroticT-Lymphocytes, RegulatoryTh1 Cells