title: Increased PD-1 on CD4(+)CD28(-) T cell and soluble PD-1 ligand-1 in patients with T2DM: association with atherosclerotic macrovascular diseases.
abstract: OBJECTIVE
  To study the role of the programmed death-1 (PD-1)/programmed death-1 ligand 1 (PD-L1) coinhibitory pathway in regulating CD4(+)CD28(-) T cells, and to explore the association of soluble PD-L1 (sPD-L1) in the development of T2DM with atherosclerotic macrovascular diseases.
  
  
  METHODS
  The percentage of CD4(+)CD28(-) T lymphocyte subsets from peripheral blood mononuclear cells (PBMCs) and the expression of PD-1/PD-L1 on lymphocytes were analyzed by immunostaining and flow cytometry, respectively. The serum levels of sPD-L1 and IFN-γ were determined by ELISA system. T cell proliferation was determined by cocultivation and WST-8 incorporation.
  
  
  RESULTS
  In 125 T2DM patients and 48 healthy donors, CD4(+)CD28(-) T cells from patients with T2DM expressed higher PD-1 than that of the cells from healthy individuals, and the proliferation response of CD4(+)CD28(-) T cells could be enhanced by advanced glycation end products (AGEs). The levels of sPD-L1 in patients were also much higher than those of healthy donors, and the increase was displayed in an exacerbation-dependent manner in the T2DM with atherosclerotic macrovascular patients especially with acute coronary syndrome (ACS). The production of sPD-L1 was significantly positively correlated with the level of IFN-γ and could enhance T cell proliferation.
  
  
  CONCLUSIONS
  Both the upregulation of PD-1 and the increase of sPD-L1 were closely associated with the severity of diabetic atherosclerotic macrovascular diseases. sPD-L1 may contribute to the continuous T cell activation and development of diabetic macrovascular diseases.
authors: Department of Endocrinology, First Affiliated Hospital of Soochow University, China.
authors: Bimin
authors: B
authors: Shi
authors: Xuan
authors: X
authors: Du
authors: Qin
authors: Q
authors: Wang
authors: Yongjing
authors: Y
authors: Chen
authors: Xueguang
authors: X
authors: Zhang
mesh_terms: D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D060890:B7-H1 Antigen / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism*; D015704:CD4 Antigens / Q000378:metabolism*; D016022:Case-Control Studies; D049109:Cell Proliferation; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D018106:CD28 Antigens; D015704:CD4 Antigens; D017127:Glycation End Products, Advanced; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor