Cd248+Cd8+T Lymphocytes Suppress Pathological Vascular Remodeling In Human Thoracic Aortic Aneurysms

Aortic aneurysms are characterized by vascular inflammation, neovascularization, and extracellular matrix destruction of the aortic wall. Although experimental studies indicate a potential role of CD248 in microvessel remodeling, the functions of CD248 in human vascular pathologies remain unexplored. Here we aimed to study how CD248 interferes with pathological vascular remodeling of human aortic aneurysms. Immunofluorescent staining showed that CD248 expression was mainly localized in the CD8+ T cells infiltrating in the adventitia and media of aortic walls of patients with ascending thoracic aortic aneurysms. qPCR and immunofluorescent staining analyses revealed increased aortic CD248 expression and infiltrating CD248+CD8+ T cells in aortic aneurysms than in nonaneurysmal aortas. Flow cytometry analysis of human peripheral blood further identified a fraction of circulating CD248+ cells which was confined in the CD8+ T-cell compartment. The increased infiltrating of CD248+CD8+ T cells was coincident with reduced circulating CD248+CD8+ T cells in patients with ascending TAA when compared with patients with coronary artery diseases and healthy donors. The CD248+CD8+ T cells were characterized by upregulated IL-10 and downregulated IL-1 beta/INF-gamma expression when compared with CD248-CD8+ T cells. Moreover, when co-cultured with human aortic endothelial cells, the CD248+CD8+ T cells not only downregulated endothelial expression of ICAM1/VCAM1 and MMP2/3 but also suppressed endothelial migration. This study shows that CD248 reduces pathological vascular remodeling via anti-inflammatory CD248+CD8+ T cells, revealing a CD248-mediated cellular mechanism against human aortic aneurysms. Impact statement In spite of recent evidence indicating that CD248 is linked to microvasculature remodeling, immune response, and MMP activity, the functions of CD248 in human TAA remain unexplored. In this work, by analyzing cellular components ofin situas well as of blood circulation of human TAA, we have identified a novel T cell subset, the CD248+CD8+ T cells, which exhibits anti-inflammatory properties, and that we have also provided the first evidence that these cells not only suppress endothelial expression of ICAM1/VCAM1 and MMP2/3, but also inhibit endothelial migration, thus uncovering a CD248-mediated cellular mechanism against pathological vascular remodeling in human aortic aneurysms.