title: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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: Beijing An Zhen Hospital, Capital Medical University; The Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education, Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
authors: Jun-Meng
authors: JM
authors: Zhang
authors: Ying
authors: Y
authors: Wang
authors: Yan-Ju
authors: YJ
authors: Miao
authors: Yi
authors: Y
authors: Zhang
authors: Yi-Na
authors: YN
authors: Wu
authors: Li-Xin
authors: LX
authors: Jia
authors: Yong-Fen
authors: YF
authors: Qi
authors: Jie
authors: J
authors: Du
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000235:genetics* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology*; D005263:Femoral Artery / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D055786:Gene Knockout Techniques; D006801:Humans; D008297:Male; D051379:Mice; D058426:Neointima / Q000378:metabolism* / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology*
chemical_list: D016827:CD8 Antigens; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha
references: Eur Heart J. 2012 Jan;33(1):120-8
references: 21733913
references: JACC Cardiovasc Interv. 2011 Oct;4(10):1057-66
references: 22017929
references: Circulation. 2008 Sep 9;118(11):1138-45
references: 18725485
references: Am J Cardiol. 2004 Jun 15;93(12):1547-9
references: 15194033
references: PLoS One. 2011;6(5):e20214
references: 21629656
references: J Am Coll Cardiol. 2006 Jul 4;48(1):193-202
references: 16814667
references: Coron Artery Dis. 2008 May;19(3):133-7
references: 18418228
references: Am J Pathol. 1994 Nov;145(5):1008-14
references: 7977633
references: Immunology. 2012 Oct;137(2):139-48
references: 22804746
references: J Mol Cell Cardiol. 2000 Nov;32(11):2097-104
references: 11040113
references: Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10530-4
references: 1961717
references: Arterioscler Thromb Vasc Biol. 2011 May;31(5):1151-9
references: 21372301
references: Cancer Res. 2005 Nov 15;65(22):10347-54
references: 16288024
references: J Am Coll Cardiol. 2010 Nov 30;56(23):1897-907
references: 21109112
references: Arterioscler Thromb Vasc Biol. 2002 Mar 1;22(3):450-5
references: 11884289
references: Anesth Analg. 2008 Aug;107(2):552-69
references: 18633035
references: J Immunol. 1991 May 1;146(9):3242-9
references: 1673149
references: Circulation. 2003 Apr 1;107(12):1658-63
references: 12668502
references: Arterioscler Thromb Vasc Biol. 2010 Aug;30(8):1576-82
references: 20489168
references: Circulation. 2011 Jun 21;123(24):2819-28, 6 p following 2828
references: 21646500
references: J Am Coll Cardiol. 2004 Aug 18;44(4):733-9
references: 15312851
references: Int J Radiat Oncol Biol Phys. 2001 Jun 1;50(2):495-501
references: 11380239
references: Arterioscler Thromb Vasc Biol. 2012 Jul;32(7):1662-74
references: 22556333
references: Am J Physiol Regul Integr Comp Physiol. 2002 Aug;283(2):R505-12
references: 12121864
references: PLoS One. 2012;7(5):e35506
references: 22567105
references: Arterioscler Thromb Vasc Biol. 2010 Dec;30(12):2467-74
references: 20884873
references: PLoS One. 2012;7(12):e51556
references: 23240042
references: Am J Physiol Cell Physiol. 2010 Dec;299(6):C1485-92
references: 20881236
references: Arterioscler Thromb Vasc Biol. 2005 Dec;25(12):2528-34
references: 16224059
references: Arterioscler Thromb Vasc Biol. 2010 Jun;30(6):1196-202
references: 20299685
references: Am J Cardiol. 2005 May 15;95(10):1146-52
references: 15877984
references: Arterioscler Thromb Vasc Biol. 1996 Jan;16(1):12-8
references: 8548411
references: Circulation. 2001 Oct 9;104(15):1754-6
references: 11591609
references: Cardiovasc Res. 2009 Dec 1;84(3):485-93
references: 19592568
references: N Engl J Med. 1986 Feb 20;314(8):488-500
references: 3511384
references: Circ Res. 1993 Nov;73(5):792-6
references: 8403250