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Table 1 Effects of tacrolimus, mycophenolate mofetil and prednisolone in tolerogenic dendritic cells generated in vitro

From: Cell therapy using tolerogenic dendritic cells in transplantation

Drugs

Models

Effects of the drugs on DC and therapeutic effects of the modified DC

References

Tacrolimus

Mouse BMDC +/− Tacrolimus

- Reduction in MHC Class I and Class II-restricted presentation of antigen (role of tacrolimus on Ag processing or presentation)

[40, 41, 43, 44]

- Reduction in pro-inflammatory cytokine (IL-6 and IL-12) secretion and expression of CD40 and CD86 by BMDC after maturation

- Tacrolimus-treated BMDC induce a low proliferation of allogeneic T cells

- Low CD69 expression and IFN-γ, IL-2 and IL-4 secretion by T cells stimulated with tacrolimus-treated BMDC

Human MoDC +/− Tacrolimus

- Low expression of CXCL10

[45–50]

- Reduction in pro-inflammatory cytokine (TNFα and IL-12) secretion by BMDC after maturation

- Decrease in CD83 and CD86 expression after LPS maturation in the presence of high levels of tacrolimus only

- Tacrolimus-treated MoDC induce a low level of allogeneic T cell proliferation, in favor of Th2 cells

- Low CD69 expression and IFN-γ, IL-2 and IL-4 secretion by T cells stimulated with tacrolimus-treated MoDC (immature or mature)

Mycophenolate mofetil

Mouse BMDC +/− MMF

- Decrease in co-stimulatory markers CD80, CD86 and CD40 expression

[51, 52]

- Decrease in IL-12 production

- MMF-treated BMDC induce a low proliferation of allogeneic T cells

- Decrease in DTH response and increase in allograft survival after injection of MMF-treated-BMDC

Human MoDC +/− MMF

- Decrease in co-stimulatory marker expression

[53]

- Induction of LPS-maturation resistance (in terms of both phenotype and cytokine release)

- MMF-treated MoDC induce a low proliferation of allogeneic T cells

- Reduction in endocytic capacity in mature MMF-treated MoDC (related to mannose receptor expression)

Prednisolone

Mouse BMDC +/− prednisolone

- IL-10/methylprednisolone-treated BMDC increase survival of skin allografts

[54]

Human MoDC +/− prednisolone

- Increase in endocytic capacity

[55–57]

- Induction of LPS maturation resistance (absence of CD80/CD86/CD83 up-regulation)

- Increase in anti-inflammatory cytokines (IL-10 and TGF-β) and decrease in pro-inflammatory cytokines (IL-6, IL-12, IL-23 and TNFα)

  

- Prednisolone-treated MoDC induce a low-level proliferation of allogeneic T cells (which acquire suppressive functions)

 
  1. BMDC: bone marrow-derived dendritic cells; CD: cluster of differentiation; CXCL10: chemokine (C-X-C motif) ligand 10; IFN-γ: interferon gamma; IL: interleukin; LPS: lipopolysaccharide; MHC: major histocompatibility complex; MMF: mycophenolate mofetil; MoDC: monocyte-derived dendritic cells; TNF α: tumor necrosis factor alpha.