title: Prope tolerance to heart allografts in mice associated with persistence of donor interleukin-10-transduced stem cells.
abstract: BACKGROUND
  We previously reported that transduction of the human interleukin (IL)-10 gene into the total fetal liver stem cells (hIL-10-TFLs) of mice protects against their rejection in an allogeneic host. In this study, we explored the effects of these cells in two different models of organ transplantation.
  
  
  METHODS
  Balb/c mice were sublethally irradiated before receiving skin or vascularized heterotopic heart grafts from C57Bl/6 mice. TFLs from C57Bl/6 mice transduced with hIL-10 or untransduced TFLs were injected on the day of transplantation into recipient mice once or also every 20 days thereafter.
  
  
  RESULTS
  Skin allograft survival was prolonged for up to 17.8±0.6 days, vs. 9.0±0.4 days, in mice that received hIL-10-TFLs or untransduced TFLs, respectively. Allogeneic heart transplants survived for 86.25±13.8, 46.3±4.6, 28.1±6.1, or 11.5±0.6 days in mice that received repeated injections of hIL-10-TFLs, a single injection of hIL-10-TFLs, repeated injections of untransduced TFLs, or controls, respectively. Histological analyses of the grafts showed fewer inflammatory foci and CD8+ infiltrating cells in mice injected with hIL-10-TFLs compared with untreated mice. Expressions of H-2b and hIL-10 were found in several organs, including the thymus, liver, and the transplant, in hIL-10-TFL-injected mice. Finally, in hIL-10-TFL-injected mice, FoxP3 T cells were present inside the transplanted heart as late as 140 days after transplantation.
  
  
  CONCLUSIONS
  In this study, we showed that repeated injections of hIL-10-TFLs are efficient in mitigating transplant rejection. This "prope" tolerance was associated with survival of donor hematopoietic cells in the host.
authors.affiliation: Transplantation and Clinical Immunology Department, Hôpital E. Herriot, Claude Bernard University, Université et Hospices Civils de Lyon, Lyon, France.
authors.forename: Leila
authors.initials: L
authors.lastname: Brikci-Nigassa
authors.forename: Masahide
authors.initials: M
authors.lastname: Matsuyama
authors.forename: Taro
authors.initials: T
authors.lastname: Hase
authors.forename: Assia
authors.initials: A
authors.lastname: Eljaafari
authors.forename: Jamel
authors.initials: J
authors.lastname: Chargui
authors.forename: Kamel
authors.initials: K
authors.lastname: Sanhadji
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Inori
authors.forename: Tatsuyama
authors.initials: T
authors.lastname: Nakatani
authors.forename: Rikio
authors.initials: R
authors.lastname: Yoshimura
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Touraine
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation / Q000276:immunology; D014161:Transduction, Genetic; D023001:Transplantation Tolerance / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C508609:IL10 protein, human; D016753:Interleukin-10