Vβ‐restricted T cell adherence to endothelial cells: A mechanism for superantigen‐dependent vascular injury

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Abstract
Objective: To investigate the potential for endothelial cells to operate as superantigen‐presenting cells for T cells and the potential for such an interaction to cause endothelial cell activation and injury.Methods: Class II major histocompatibility complex (MHC)–positive human umbilical vein endothelial cells (HUVECs) were cocultured for 4 hours with purified T cells and the superantigens staphylococcal enterotoxin B (SEB) or toxic shock syndrome toxin 1 (TSST‐1). After staining with fluorescence‐conjugated monoclonal antibodies, flow cytometric analysis was performed on the HUVECs and T cells to examine Vβ‐restricted T cell adherence to the endothelial cell monolayer, Vβ‐restricted T cell activation (CD69 up‐regulation), surface expression of endothelial cell activation markers, and generation of endothelial microparticles (EMPs).Results: Coculture of purified T cells with class II MHC–positive HUVECs and either TSST‐1 or SEB resulted in Vβ‐restricted CD69 up‐regulation by CD4 and CD8 cells (Vβ2 activation for TSST‐1; Vβ3, Vβ5.1, and Vβ12 activation for SEB). Additionally, there was CD4 and CD8 T cell Vβ‐restricted adherence to the HUVEC monolayer at 4 hours. Expression of intercellular adhesion molecule 1, E‐selectin, and vascular cell adhesion molecule 1 was up‐regulated on the class II MHC–positive HUVECs following exposure to superantigen in the presence of T cells, and there was increased EMP release from activated HUVECs, which occurred earlier and was of greater magnitude than that observed in response to tumor necrosis factor α.Conclusion: Class II MHC–positive endothelial cells operate as competent superantigen‐presenting cells for CD4 and CD8 lymphocytes in vitro. Dual signaling between endothelial cells and T cells results in Vβ‐restricted activation and adherence to endothelial monolayers and endothelial cell activation and release of EMPs expressing inducible cell adhesion molecules. It is proposed that this mechanism could account in part for the vascular injury associated with superantigen‐mediated diseases including Kawasaki disease.

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