Knockout of CD8 Delays Reendothelialization and Accelerates Neointima Formation in Injured Arteries of Mouse via TNF-α Inhibiting the Endothelial Cells Migration

ObjectiveDelayed or impaired reendothelialization is a major cause of stent thrombosis in the interventional treatment of coronary heart disease. T cells are involved in neointima formation of injured arteries. However, the regulated mechanism of reendothelialization and the role of CD8 T cell in reendothelialization are unclear.Methods and ResultsImmunofluorescence staining showed that CD8 positive cells were increased in wire injured femoral artery of mice. On day 21 after injury, elastin staining showed that knockout of CD8 (CD8−/−) significantly increased intimal thickness and a ratio of intima to media by 1.8 folds and 1.9 folds respectively in injured arteries. Evans blue staining showed that knockout of CD8 delayed the reendothelialization area on day 7 after injury (18.8±0.5% versus 42.1±5.6%, pIn vitro, a migration assay revealed that CD8−/− T cells co-cultured with WT macrophages significantly inhibited the migration of the endothelial cells (ECs); compared to CD4+ T cells, and CD8+ T cells could promote the ECs migration. Furthermore, real-time PCR analysis showed that knockout of CD8 increased the level of tumor necrosis factor α (TNF-α) in injured arteries and cytometric bead cytokine array showed that TNF-α was elevated in cultured CD8−/− T cells. Finally, a wound-healing assay showed that recombinant TNF-α significantly inhibited the migration of ECs.ConclusionOur study suggested that CD8+ T cells could promote the reendothelialization and inhibit the neointima formation after the artery wire injury, and this effect is at least partly dependent on decreasing TNF-α production promoting ECs migration.