CD57+ T Cell Transmigration Through Vascular Endothelial Cells is Enhanced by Tumor Necrosis Factor: A Novel Model of Cardiovascular Risk in People with HIV

Abstract

People with human immunodeficiency virus (PWH), despite achieving viral suppression through antiretroviral therapy, face increased risk and earlier onset of atherosclerotic cardiovascular diseases than the general population. CD57+ T cells can be readily recovered from atherosclerotic plaques and likely contribute to disease by targeting endothelial cells (ECs); however, the specific mechanisms facilitating the infiltration of these cells into plaques remain elusive. Here, we report the development of a novel assay to quantify T cell adhesion to and transmigration through a primary human vascular EC monolayer and show that CD57+ T cells preferentially adhere to and transmigrate through the monolayer. Moreover, activating the ECs with tumor necrosis factor (TNF) significantly increased the transmigration of CD57+ T cells, supporting the role of TNF in promoting the vascular homing of CD57+ T cells. This model will allow for elucidating the mechanisms of and testing interventions to prevent CD57+ T cell infiltration into plaques.