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. 2020 Sep 25;16(9):e1008885. doi: 10.1371/journal.ppat.1008885

Fig 7. Model linking CX3CR1+ CD8 T cells, TNF, and IL-15 to endothelial dysfunction and vascular inflammation.

Fig 7

(1) Endothelial cell activation/dysfunction is induced by viral infection, bacterial products, and/or proinflammatory cytokines and lipids; (2) Activated endothelial cells express and release CX3CL1 and IL-15; (3) IL-15 activates CD8 T cells by arming them with the cytolytic molecules, promoting CX3CR1 expression, and increasing TNF production; (4) CX3CL1/CX3CR1 interactions promote CD8 T cell migration and tethering to the activated endothelium, where the cells release TNF and lytic granules like granzyme B and perforin; (5) TNF and endothelial damage further increase CX3CL1 and bioactive IL-15 expression by vascular endothelial cells creating a positive proinflammatory feedback loop that facilitates continued endothelial cell activation, damage, and accumulation of activated CD8 T cells in the subendothelium. These changes may promote atherogenesis in HIV infection and in HIV-uninfected individuals with persistent vascular inflammation.