Low-dose of tacrolimus favors the induction of functional CD4+CD25+FoxP3+ regulatory T cells in solid-organ transplantation

Impact of immunosuppressive drugs on the therapeutic efficacy of ex vivo expanded human regulatory T cells

“…This inhibition, previously described with T lymphocytes, 33 may aggravate even more the already critical Treg survival during immunosuppressive drug administration. Although previous data suggested that the treatment of transplant recipients with low doses of TAC may be beneficial to Tregs, 34 there are many other studies providing evidence of the potentially harmful effect of calcineurin inhibitors on human Tregs. [35][36][37] Although, we have not found any evidence of a negative effect of TAC on the FOXP3 expression, function and stability of our Treg preparations, some studies in animal models reported that CsA treatment reduced Foxp3 expression in natural Tregs, 32,38 40 In addition, calcineurin inhibitors have been shown to affect Treg stability by directly interfering with NFAT signaling, and, as a consequence, its interaction with FOXP3.…”

Factors associated with severe versus mild immunotherapy-related systemic reactions: A case-referent study

“…Although this issue was not addressed in this study, some studies showed the expansion of the peripheral regulatory T (Treg) cell population in tacrolimus-treated patients. 11 However, our group has recently reported a significantly more rapid onset of FA in children treated with tacrolimus and basiliximab compared with that seen in children receiving tacrolimus and prednisone. 7 In children receiving basiliximab, the total pool of Treg cells did not change, but it was suggested that Treg cell function was altered in the absence of functional CD25.…”

After Moving of Regulatory T-Cell Therapy to the Clinic: Will We Need a New Tregs Source?

“…59 On the other hand, MMF and lowdose tacrolimus had an induction of CD4+CD25+FOXP3+ Tregs as showed in kidney transplanted recipients treated with these drugs that permit Tregs expansion in the periphery and accumulation in the allograft and the maintenance of their suppressive function which was confirmed by in vitro analysis of these cells. 60 Other studies showed that MMF has no effect on Tregs numbers and function but may facilitate the induction of a more tolerogenic environment. 58 Many researchers described the positive effects of dexamethasone and prednisolone on expansion of Tregs by the IL-2-dependent expansion of FOXP3+CD4+CD25+ T cells 61 or maturation of Tregs by increasing FOXP3 expression, 62 and restore the impaired suppressive function of Tregs.…”