title: Unique effects of mycophenolate mofetil on cord blood T cells: implications for GVHD prophylaxis.
abstract: BACKGROUND
  Hematopoietic stem cell transplantation (HSCT) is a common treatment for hematological diseases. Cord blood (CB) is increasingly used as a source of stem cells for HSCT. Prophylactic drugs, such as mycophenolate mofetil (MMF) and cyclosporine A (CsA), are often used together after HSCT to prevent graft-versus-host disease (GvHD), but so far little is known about their effects on CB mononuclear cells (CBMCs). As CB and peripheral blood (PB) have different cell compositions and characteristics, it was hypothesized that MMF and CsA might have different effects on CB and PB T cells.
  
  
  METHODS
  Using a combination of flow cytometry, ELISA, and quantitative PCR, the effects of MMF, CsA, and the combination of both drugs were studied on resting and activated CBMCs and peripheral blood mononuclear cells.
  
  
  RESULTS
  MMF had a stronger effect on activated PB T cells than on activated CB T cells, which was consistent with the lower level of IMPDH2 mRNA expressed by PB T cells. Interestingly, only MMF could preserve the activated CB regulatory T-cell population. Activated CB T cells were more sensitive to CsA than activated PB T cells, which might be explained by the lower NFATc1 expression and cytokine secretion. These results may explain the lower GvHD incidence observed in recipients of CB transplants.
  
  
  CONCLUSIONS
  This study provides valuable insight into the effects of immunosuppressive drugs used after HSCT on resting and activated T-cell subsets from PB but especially from CB.
authors.affiliation: 1 Anthony Nolan Research Institute and University College London, London, UK. 2 Address correspondence to: Aurore Saudemont, Ph.D., Anthony Nolan Research Institute, Fleet Road, NW3 2QG London, UK.
authors.forename: Sophie
authors.initials: S
authors.lastname: Derniame
authors.forename: Fuiyee
authors.initials: F
authors.lastname: Lee
authors.forename: Anna
authors.initials: A
authors.lastname: Domogala
authors.forename: Alejandro
authors.initials: A
authors.lastname: Madrigal
authors.forename: Aurore
authors.initials: A
authors.lastname: Saudemont
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D036101:Cord Blood Stem Cell Transplantation; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016572:Cyclosporine; D016207:Cytokines; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D009173:Mycophenolic Acid; D000099192:CD69 Antigens; C508017:IL2RA protein, human