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 (TCR) 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 (PSGL-1) receptor. In experimental atherosclerosis the aorta supports CD4+ T cell activation selectively driving Th1 polarization. By contrast, secondary lymphoid organs display Treg expansion. CONCLUSIONS: 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.