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: Rapa-mDCs re-educate the inflammatory microenvironment, promoting skin-allograft survival.
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:Rapa-mDCs re-educate the inflammatory microenvironment, promoting skin-allograft survival.
Entities:
Keywords:
cellular therapy; dendritic cells; regulatory T cells; tolerance