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.
The aorta can act as a site of naïve CD4+ T-cell priming / 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, Claudia; Maffia, P.. - In: CARDIOVASCULAR RESEARCH. - ISSN 0008-6363. - 116:2(2020), pp. 306-316. [10.1093/cvr/cvz102]
The aorta can act as a site of naïve CD4+ T-cell priming
Grassia G.Investigation
;Garside P.;Maffia P.
Project Administration
2020
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.File | Dimensione | Formato | |
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