Knockout of CD8 delays reendothelialization and accelerates neointima formation in injured arteries of mouse via TNF-α inhibiting the endothelial cells migration.

Abstract

OBJECTIVE:

Delayed 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 RESULTS:

Immunofluorescence 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%, p<0.05). In 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.

CONCLUSION:

Our 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.

• Authors: Jun-Meng Zhang, Ying Wang, Yan-Ju Miao, Yi Zhang, Yi-Na Wu, Li-Xin Jia, Yong-Fen Qi, Jie Du
• Journal: PloS one (PLoS One) Vol. 8 Issue 5 Pg. e62001 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23658704 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD8 Antigens
• Recombinant Proteins
• Tumor Necrosis Factor-alpha

Topics

• Animals
• CD8 Antigens (genetics, metabolism)
• CD8-Positive T-Lymphocytes (drug effects, metabolism)
• Cell Movement (drug effects)
• Endothelial Cells (drug effects, pathology)
• Femoral Artery (drug effects, injuries, metabolism, pathology)
• Gene Deletion
• Gene Knockout Techniques
• Humans
• Male
• Mice
• Neointima (metabolism, pathology)
• Recombinant Proteins (pharmacology)
• Time Factors
• Tumor Necrosis Factor-alpha (biosynthesis, pharmacology)