Artículo de revista
Rapamycin-conditioned dendritic cells activated with monophosphoryl lipid-A promote allograft acceptance in vivo
Fecha
2015Registro en:
Immunotherapy (2015) 7(2), 101–110
17507448
1750743X
10.2217/imt.14.116
Autor
Campos Acuña, Javier
Pérez, Francisco
Narváez, Edgar
Campos Mora, Mauricio
Gajardo, Tania
Catalán Martina, Diego
Aguillón Gutiérrez, Juan Carlos
Pino Lagos, Karina
Institución
Resumen
Aim: 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. Materials & 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. Conclusion: RapamDCs re-educate the inflammatory microenvironment, promoting skin-allograft
survival.