title: Overexpression of programmed death ligand 1 in dendritic cells inhibits allogeneic lymphocyte activation in mice.
abstract: BACKGROUND
  Co-stimulatory molecules are pivotal for T cell activation. It is increasingly recognized that programmed death ligand 1 (PD-L1) is a novel co-stimulatory molecule, which raises the question as to whether PD-L1 regulates T cell responses. This study aimed to investigate the inhibitory effects of PD-L1 on T cell activation.
  
  
  METHODS
  We constructed a transgenic vector containing the complete PD-L1 gene, which interacts with the inhibitory receptor PD-1 in T cell-mediated immune activation. Donor dendritic cells (DCs) derived from C57BL/6 mice were transfected with PD-L1 and mixed with allogeneic, recipient T cells from BALB/c mice. The T cell activation was determined by the MTT assay and T cell proliferation was determined using carboxyfluoroscein succinimidyl ester (CFSE)-labeling following in vitro mixed leukocyte reactions.
  
  
  RESULTS
  The expression of PD-L1 protein in PD-L1-transfected DCs was 47.97% ± 1.06%, compared with 4.66% ± 0.76% and 5.30% ± 0.60% in blank and negative controls, respectively (P < 0.05). PD-L1 protein was effectively expressed in DCs. Furthermore, in DCs stably transfected with PD-L1, T cell activation was significantly suppressed and T cell proliferation rate was decreased by 35% compared with untransfected DCs (P < 0.05).
  
  
  CONCLUSIONS
  PD-L1 delivers an immunoinhibitory signal, suppressing T cell activation. Overexpression of PD-L1 signaling induces tolerance, which presents a promising immunotherapeutic approach for long-term graft acceptance.
authors.affiliation: Department of Urology, Jinshan Hospital, Fudan University, Shanghai, China.
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Li
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.forename: Renfu
authors.initials: R
authors.lastname: Chen
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhu
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000235:genetics* / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D015870:Gene Expression / Q000502:physiology; D007108:Immune Tolerance / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D019076:Transgenes / Q000235:genetics; D014181:Transplantation Immunology / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse