title: Human umbilical vein endothelial cells promote the inhibitory activation of CD4(+)CD25(+)Foxp3(+) regulatory T cells via PD-L1.
abstract: BACKGROUND
  Atherosclerosis (AS) is a chronic inflammation characterized by massive infiltration of inflammatory cells in arterial wall plaques. Programmed death ligand-1 (PD-L1), a co-stimulatory molecule, plays a vital role in regulating immune responses. We investigated the role and mechanisms of PD-L1 expressed on oxidized low-density lipoprotein (ox-LDL)-impaired human umbilical vein endothelial cells (HUVECs) in promoting activation and cytokine production of CD4(+)CD25(+) forkhead box P3 (FoxP3) regulatory T cells (Tregs).
  
  
  RESULTS
  Tregs were incubated alone, with HUVECs or HUVECs pre-stimulated with ox-LDL in the presence of anti-CD3 monoclonal antibodies (mAbs) for 48 h. HUVECs were shown to upregulate the immune phenotypic markers of Tregs, such as glucocorticoid-induced TNF receptor (GITR), cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 protein (PD-1). Moreover, HUVECs modulated cytokine production of Tregs (e.g., interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1)). HUVECs treated with anti-PD-L1 mAbs were unable to regulate the surface expression and cytokine production of Tregs. The Transwell culture system suggested that interaction between HUVECs and Tregs via PD-L1 requires cell-to-cell contact.
  
  
  CONCLUSIONS
  Expression of the negative co-stimulatory molecule PD-L1 on HUVECs may upregulate the inhibitory activation and cytokine production of CD4(+)CD25(+)Foxp3(+) regulatory T cells in AS.
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiao-Fan
authors.initials: XF
authors.lastname: Hu
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yan
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Wen-Yong
authors.initials: WY
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Mao
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China. Electronic address: shuyanwen@yahoo.com.
authors.forename: Yan-Wen
authors.initials: YW
authors.lastname: Shu
mesh_terms: D000293:Adolescent; D000328:Adult; D050197:Atherosclerosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology* / Q000378:metabolism; D008297:Male; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis / Q000235:genetics*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D055815:Young Adult
chemical_list: D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Atherosclerosis; Endothelial cells; Programmed death ligand-1; Regulatory T cells