title: Corticosteroids do not reverse the inhibitory effect of cyclosporine on regulatory T-cell activity in contrast to mycophenolate mofetil.
abstract: BACKGROUND
  Inevitable hepatitis C virus recurrence after liver transplantation, a major barrier to survival of the transplanted liver may be promoted by immunosuppression and by CD4(+)CD25(+) regulatory T cells (Treg). Treg cells are essential for the induction and maintenance of immunologic self-tolerance as well as transplant tolerance. Moreover, we have previously described low doses of cyclosporine (CsA) to inhibit Treg activity by inducing interleukin-2 and interfron-γ. We investigated here in, the effect of mycophenolate mofetil (MMF) and corticosteroids, usually used in combination with a calcineurin inhibitor on human CD4(+)CD25(+) Treg cells.
  
  
  METHODS
  Human CD4(+)CD25(+) cells isolated from healthy donors were cultured in the presence of CsA +/- corticoids or MMF. Suppressive activity of regulatory T cells was assessed in mixed leukocyte reactions including CD25(+) solvents with autologous activated peripheral blood mononuclear cells (PBMC).
  
  
  RESULTS
  MMF and dexamethasone inhibited PBMC and Treg proliferation in dose-dependent fashing, maintaining the suppressive activity of Treg cells. However, the association of corticoids with CsA could not reverse the inhibitory effects of CsA on Treg activity, unlike the MMF and CsA combination.
  
  
  CONCLUSIONS
  We have previously shown CsA to significantly impair the function of CD4(+)CD25(+) Treg cells. Herein we reports that corticoids were not able to reverse this effect, whereas MMF couterbalanced it, suggesting that the combination of MMF with CsA maintains regulatory T cells activity promoting tolerance.
authors.affiliation: CNRS-UMR 8161-Institut de Biologie de Lille, Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Miroux
authors.forename: O
authors.initials: O
authors.lastname: Morales
authors.forename: L
authors.initials: L
authors.lastname: Ouaguia
authors.forename: L
authors.initials: L
authors.lastname: Aoudjehane
authors.forename: E
authors.initials: E
authors.lastname: Boleslawski
authors.forename: V
authors.initials: V
authors.lastname: Pancré
authors.forename: Y
authors.initials: Y
authors.lastname: de Launoit
authors.forename: Y
authors.initials: Y
authors.lastname: Calmus
authors.forename: F
authors.initials: F
authors.lastname: Conti
authors.forename: N
authors.initials: N
authors.lastname: Delhem
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D065095:Calcineurin Inhibitors; C508017:IL2RA protein, human; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D003907:Dexamethasone; D016572:Cyclosporine; D019703:Calcineurin; D009173:Mycophenolic Acid