title: Prolongation of the rat composite tissue allograft survival by the combination of tolerogenic immature dendritic cells and short-term treatment with FK506.
abstract: OBJECTIVE
  Prevention of rejection in composite tissue allotransplantation without continuous immunosuppression is of paramount importance in the field of transplantation. Recently dendritic cells (DCs) have gained considerable attention as antigen-presenting cells that are also capable of tolerance induction. This study assessed the effect of interleukin (IL)-10-supplemented, alloantigen-pulsed immature tolerogenic DC to increase survival of orthotopic hind limb transplantations in rats.
  
  
  METHODS
  Hind limbs from Sprague-Dawley (SD) hosts were transplanted to Fischer 344 (F344) rats. Peripheral blood mononuclear cells (PBMC) isolated from F344 were cultured to generate immature DCs (imDCs); IL-10 was added for tolerogenic DC induction. Flow cytometric analysis were performed to characterize the DC phenotype. IL-10-imDCs cocultured with donor mononuclear cells for 24 hours were reinjected into recipients subcutaneously 1 day before transplantation. Recipient animals were divided into 4 groups, each comprising 6 rats (n = 6): group I (untreated controls), group II (IL-10-imDCs alone), group III (FK-506 [Tacrolimus, 2 mg/kg] for 2 weeks postoperative), and group IV (recipient origin IL-10-imDCs combined with FK-506 for 2 weeks postoperative). Observation of graft appearance, cytokine production assays, and confocal immunofluorescence were performed at postoperative 1 week.
  
  
  RESULTS
  The combination of IL-10-treated imDCs and FK-506 produced a significantly prolonged median allograft survival (46.7 days) compared with groups I (4.7), II (5.3), or III (26.3). Splenocytes isolated from rats treated with IL-10-imDCs plus and FK-506 produced significant amounts of IL-10 and IL-4 cytokines upon alloantigen stimulation, as confirmed using ELISPOT and ELISA.
  
  
  CONCLUSIONS
  We demonstrated that IL-10-treated imDCs induced T-cell hyporesponsiveness, skewing the immune response to Th2 elements, resulting in long-term survival of composite tissue allografts.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Cancer Research Institute, Tumor Immunity Medical Research Center, Xenotransplantation Research Center, Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: S-C
authors.initials: SC
authors.lastname: Eun
authors.forename: R-M
authors.initials: RM
authors.lastname: Baek
authors.forename: C-G
authors.initials: CG
authors.lastname: Park
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D006085:Graft Survival; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000008:administration & dosage*; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus