Tight control – decision-making during T cell–vascular endothelial cell interaction

Sonja Firner, Lucas Onder, Veronika Nindl, Burkhard Ludewig

Vascular endothelial cells (ECs) form the inner layer of blood vessels and exert crucial functions during immune reactions including coagulation, inflammation, and regulation of innate immunity. Importantly, ECs can interact with T cells in an antigen-specific, i.e., T cell receptor-dependent manner. In this review, we will discuss EC actions and reactions during acute inflammation and focus on the interaction of T cells with ECs at two vascular sites: the high endothelial venule (HEV) of lymph nodes, and the vascular lesion during transplant vasculopathy (TV). HEVs are characterized by a highly active endothelium that produces chemoattracting factors and expresses adhesion molecules to facilitate transit of lymphocytes into the lymph node (LN) parenchyma. Yet, T cell-EC interaction at this anatomical location results neither in T cell activation nor tolerization. In contrast, the endothelium at sites of chronic inflammation, such as solid organ transplants, can promote T cell activation by upregulation of major histocompatibility complex (MHC) and costimulatory molecules. Importantly, a major function of ECs in inflamed tissues must be the maintenance of vascular integrity including the efficient attenuation of effector T cells that may damage the vascular bed. Thus, antigen-specific T cell-EC interaction is characterized by a tightly controlled balance between immunological ignorance, immune activation, and tolerization.