title: Transplantation of NIT-1 cells expressing pD-L1 for treatment of streptozotocin-induced diabetes.
abstract: BACKGROUND
  Programmed death-1 ligand-1 (PD-L1, CD274, B7-H1) has been identified as the ligand for the immunoinhibitory receptor programmed death-1 and has been demonstrated to play a role in the regulation of immune responses and peripheral tolerance. In this study, we tested the effect of PD-L1-transfected pancreatic beta-cell line established from a transgenic NDD/Lt mouse (NIT) on the alloresponse and streptozotocin-induced diabetes.
  
  
  METHODS
  The diabetes model was established by a low dose of streptozotocin in Balb/C mice. PD-L1 transfected NIT cell line was established, namely NIT-PD-L1. NIT-1, empty vector-transfected NIT-1, or NIT-PD-L1 cells were transplanted into diabetic mice by intraperitoneal injection, respectively. Proliferation and apoptosis of splenic lymphocytes were detected by labeling with carboxy fluorescein succinimidyl ester or AnnexinV-Cy5 and proliferation index (PI). Cytokines were determined by enzyme-linked immunosorbent assay and flow cytometry analysis.
  
  
  RESULTS
  When compared with the controls, overexpression of PD-L1 on NIT-1 cells markedly prolonged allograft survival in diabetic mice. In mixed cells reaction, splenic lymphocytes from NIT-PD-L1-transplanted diabetic mice co-culture with mitomycin C-treated NIT-PD-L1 showed the lowest proliferative response but severe apoptosis. In addition, NIT-PD-L1 suppressed interferon-gamma but up-regulated interleukin-4 and -10 productions by those lymphocytes in vitro and in vivo.
  
  
  CONCLUSIONS
  Our data demonstrated that overexpression of PD-L1 on pancreatic beta cells significantly can prolong allograft survival, and it is associated with inhibition of lymphocytes activation and proliferation, induction of lymphocytes apoptosis.
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wen
authors.forename: Huifen
authors.initials: H
authors.lastname: Zhu
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Daofeng
authors.initials: D
authors.lastname: Yang
authors.forename: Wenjun
authors.initials: W
authors.lastname: Liao
authors.forename: Guanxin
authors.initials: G
authors.lastname: Shen
mesh_terms: D000818:Animals; D017209:Apoptosis; D018122:B7-1 Antigen / Q000378:metabolism*; D060890:B7-H1 Antigen; D018920:Coculture Techniques; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000628:therapy*; D005260:Female; D006085:Graft Survival; D050417:Insulin-Secreting Cells / Q000166:cytology*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008024:Ligands; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D016685:Mitomycin / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism*
chemical_list: D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D010455:Peptides; D016685:Mitomycin