title: Rapamycin-conditioned dendritic cells activated with monophosphoryl lipid-A promote allograft acceptance in vivo.
abstract: OBJECTIVE
  To date, there is no human dendritic cell (DC) based therapy to prevent allograft rejection in transplanted patients. Here, we evaluate a potential protocol using a murine in vivo transplant model.
  
  
  METHODS
  We generated murine bone marrow-derived DCs (BM-DCs), modulated with rapamycin (Rapa) and activated with monophosphoryl lipid A (Rapamycin-treated and monophosphoryl lipid A-matured DCs [Rapa-mDCs]). DCs phenotype was evaluated by flow cytometry, cytokine production by ELISA and their T-cell stimulatory ability was tested in co-cultures with CD4(+) T cells. Using an in vivo skin graft model, we evaluated DCs tolerogenicity.
  
  
  RESULTS
  In vitro, Rapa-mDCs exhibit a semi-mature phenotype given by intermediate levels of co-stimulatory molecules and cytokines, and inhibit CD4(+) T-cell proliferation. In vivo, skin-grafted mice treated with Rapa-mDCs show high allograft survival, accumulation of Foxp3(+) Tregs and cytokine pattern modification.
  
  
  CONCLUSIONS
  Rapa-mDCs re-educate the inflammatory microenvironment, promoting skin-allograft survival.
authors.affiliation: Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Av. Independencia 1027, 3er Piso, Pabellon I, Santiago 8380453, Chile.
authors.forename: Javier
authors.initials: J
authors.lastname: Campos-Acuña
authors.forename: Francisco
authors.initials: F
authors.lastname: Pérez
authors.forename: Edgar
authors.initials: E
authors.lastname: Narváez
authors.forename: Mauricio
authors.initials: M
authors.lastname: Campos-Mora
authors.forename: Tania
authors.initials: T
authors.lastname: Gajardo
authors.forename: Diego
authors.initials: D
authors.lastname: Catalán
authors.forename: Juan C
authors.initials: JC
authors.lastname: Aguillón
authors.forename: Karina
authors.initials: K
authors.lastname: Pino-Lagos
mesh_terms: D064591:Allografts; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D020123:Sirolimus / Q000494:pharmacology*; D016038:Skin Transplantation
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D008050:Lipid A; C048436:monophosphoryl lipid A; D020123:Sirolimus
keywords: cellular therapy; dendritic cells; regulatory T cells; tolerance