title: Rapid tolerance induction by hematopoietic progenitor cells in the absence of donor-matched lymphoid cells.
abstract: BACKGROUND
  Donor specific hematopoietic cell transplantation has long been recognized for its potential in tolerance induction for subsequently transplanted organs. We have recently published that co-administration of Myeloid Progenitor (MP) and third party Hematopoietic Stem Cells (HSC) can induce MP-specific tolerance for subsequently transplanted organs [1].
  
  
  METHODS
  Mice received an allogeneic HSC and third party MP transplantation simultaneous with placement of a MP-matched skin graft. Variants tested include time of graft placement, MP genotype and source of cells.
  
  
  RESULTS
  Using B10;B6-Rag2(-/-)Il2rg(-/-) mice, we demonstrate that specific tolerance can be induced by MP given simultaneous with the skin graft in the complete absence of MP-donor-matched lymphoid cells. Ex vivo expanded MP function as well as sorted cells in inducing tolerance. In addition we demonstrate that tolerance can be induced by MP in the context of autologous HSC transplantation.
  
  
  CONCLUSIONS
  Our results demonstrate that the previously observed expansion of organ donor matched Treg is not essential for tolerance, and that MP tolerance protocols can be envisioned in most clinical settings, including those involving deceased donor organs.
authors.affiliation: Section of Cardiac Surgery, Children's Mercy Hospital and Clinics, Kansas City MO64108, United States; Department of Pediatrics, University of Missouri Kansas City, Kansas City, MO, United States. Electronic address: adomen@cmh.edu.
authors.forename: Jos
authors.initials: J
authors.lastname: Domen
authors.affiliation: Section of Cardiac Surgery, Children's Mercy Hospital and Clinics, Kansas City MO64108, United States. Electronic address: yli@cmh.edu.
authors.forename: Yongwu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Section of Cardiac Surgery, Children's Mercy Hospital and Clinics, Kansas City MO64108, United States. Electronic address: lsun@cmh.edu.
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States. Electronic address: psimpson@mcw.edu.
authors.forename: Pippa
authors.initials: P
authors.lastname: Simpson
authors.affiliation: Section of Cardiac Surgery, Children's Mercy Hospital and Clinics, Kansas City MO64108, United States; Department of Pediatrics, University of Missouri Kansas City, Kansas City, MO, United States; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States. Electronic address: gandyk@umkc.edu.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Gandy
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics; D046148:Donor Selection; D051858:Forkhead Transcription Factors / Q000235:genetics; D006085:Graft Survival / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023461:Myeloid Progenitor Cells / Q000276:immunology / Q000637:transplantation*; D016038:Skin Transplantation / Q000379:methods*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; C499308:Rag2 protein, mouse
keywords: Hematopoietic stem cell; Myeloid progenitor; Rodent; Tolerance; Transplantation