title: Impaired thymic export and increased apoptosis account for regulatory T cell defects in patients with non-ST segment elevation acute coronary syndrome.
abstract: Regulatory T (Treg) cells play a protective role against the development of atherosclerosis. Previous studies have revealed Treg cell defects in patients with non-ST elevation acute coronary syndrome (NSTACS), but the mechanisms underlying these defects remain unclear. In this study, we found that the numbers of peripheral blood CD4(+)CD25(+)CD127(low) Treg cells and CD4(+)CD25(+)CD127(low)CD45RA(+)CD45RO(-) naive Treg cells were lower in the NSTACS patients than in the chronic stable angina (CSA) and the chest pain syndrome (CPS) patients. However, the number of CD4(+)CD25(+)CD127(low)CD45RA(-)CD45RO(+) memory Treg cells was comparable in all of the groups. The frequency of CD4(+)CD25(+)CD127(low)CD45RO(-)CD45RA(+)CD31(+) recent thymic emigrant Treg cells and the T cell receptor excision circle content of purified Treg cells were lower in the NSTACS patients than in the CSA patients and the CPS controls. The spontaneous apoptosis of Treg cells (defined as CD4(+)CD25(+)CD127(low)annexin V(+)7-AAD(-)) was increased in the NSTACS patients compared with the CSA and CPS groups. Furthermore, oxidized LDL could induce Treg cell apoptosis, and the oxidized LDL levels were significantly higher in the NSTACS patients than in the CSA and CPS groups. In accordance with the altered Treg cell levels, the concentration of TNF-α was increased in the NSTACS patients, resulting in a decreased IL-10/TNF-α ratio. These findings indicate that the impaired thymic output of Treg cells and their enhanced susceptibility to apoptosis in the periphery were responsible for Treg cell defects observed in the NSTACS patients.
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Wen-cai
authors.initials: WC
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Yan-wen
authors.initials: YW
authors.lastname: Shu
authors.forename: Ting-ting
authors.initials: TT
authors.lastname: Tang
authors.forename: Zheng-feng
authors.initials: ZF
authors.lastname: Zhu
authors.forename: Ni
authors.initials: N
authors.lastname: Xia
authors.forename: Shao-fang
authors.initials: SF
authors.lastname: Nie
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Su-feng
authors.initials: SF
authors.lastname: Zhou
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Xiao
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.forename: Meng-yang
authors.initials: MY
authors.lastname: Liao
authors.forename: Long-xian
authors.initials: LX
authors.lastname: Cheng
authors.forename: Yu-hua
authors.initials: YH
authors.lastname: Liao
authors.forename: Xiang
authors.initials: X
authors.lastname: Cheng
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000235:genetics / Q000276:immunology; D000368:Aged; D015703:Antigens, CD / Q000097:blood / Q000276:immunology; D017209:Apoptosis; D001692:Biological Transport / Q000276:immunology; D005260:Female; D006801:Humans; D017370:Interleukin-11 / Q000097:blood / Q000276:immunology; D008077:Lipoproteins, LDL / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology
chemical_list: D015703:Antigens, CD; C508611:IL11 protein, human; D017370:Interleukin-11; D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein