title: Allogenicity of human cardiac stem/progenitor cells orchestrated by programmed death ligand 1.
abstract: BACKGROUND
  Transplantation of allogeneic cardiac stem/progenitor cells (CPC) in experimental myocardial infarction promoted cardiac regeneration and improved heart function. Although this has enhanced prospects of using allogeneic CPC for cardiac repair, the mechanisms regulating the behavior of these allogeneic cells, which are central to clinical applications, remain poorly understood.
  
  
  OBJECTIVE
  T cells orchestrate the allogeneic adaptive immune response. Therefore, to provide insight into the mechanisms regulating the immunologic behavior of human CPC (hCPC), we investigated the allogeneic T-cell response elicited by cryopreserved c-kit-selected hCPC.
  
  
  RESULTS
  By using an experimental model of allogeneic stimulation, we demonstrate that, whether under inflammatory conditions or not, hCPC do not trigger conventional allogeneic Th1 or Th2 type responses but instead induce proliferation and selective expansion of suppressive CD25(high)CD127(low)human leukocyte antigen-DR(+)FoxP3(high) effector regulatory T cells. The regulatory T-cell proliferation and amplification were dependent on the interaction with the B7 family member programmed death ligand 1 (PD-L1), which is substantially expressed on hCPC and increased under inflammatory conditions. Thus, hCPC in allogeneic settings acquire the capacity to downregulate an ongoing immune response, which was dependent on PD-L1.
  
  
  CONCLUSIONS
  Collectively, these data reveal that hCPC in allogeneic settings have a tolerogenic immune behavior, promoting a contact PD-L1-dependent regulatory response and a PD-L1-dependent allogeneic-driven immunomodulation. Our study attributes an important role for PD-L1 in the immune behavior of allogeneic hCPC and raises the possibility of using PD-L1 expression as a marker to identify and select low-risk high-benefit allogeneic cardiac repair cells.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale UMRS940, Institut Universitaire d’Hématologie, Université Paris-Diderot and Laboratoire d’Immunologie et d’Histocompatibilité, Hôpital Saint Louis, Paris, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Lauden
authors.forename: Wahid
authors.initials: W
authors.lastname: Boukouaci
authors.forename: Luis R
authors.initials: LR
authors.lastname: Borlado
authors.forename: Itziar Palacios
authors.initials: IP
authors.lastname: López
authors.forename: Pilar
authors.initials: P
authors.lastname: Sepúlveda
authors.forename: Ryad
authors.initials: R
authors.lastname: Tamouza
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.forename: Reem
authors.initials: R
authors.lastname: Al-Daccak
mesh_terms: D056704:Adaptive Immunity; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002450:Cell Communication; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D015925:Cryopreservation; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation; D032383:Myocytes, Cardiac / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D034622:RNA Interference; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D014162:Transfection
chemical_list: D060890:B7-H1 Antigen; D015415:Biomarkers; C423236:CD274 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006684:HLA-DR Antigens; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D019009:Proto-Oncogene Proteins c-kit