title: T-cell reactivity during tapering of immunosuppression to low-dose monotherapy prednisolone in HLA-identical living-related renal transplant recipients.
abstract: BACKGROUND
  In many transplant centers, human leukocyte antigen (HLA)-identical living-related (LR) renal transplant recipients receive standard maintenance immunosuppression from 1 year after transplantation. We questioned whether discontinuation of azathioprine (AZA) or mycophenolate mofetil (MMF) influenced T-cell reactivity, circulating dendritic cell (DC) subsets numbers and their maturation status.
  
  
  METHODS
  Twenty-nine HLA-identical LR renal transplant recipients were withdrawn from AZA or MMF. Thereafter, the patients received only prednisolone. T-cell reactivity was determined by interferon-gamma (n=23), interleukin (IL)-10 (n=16), and granzyme B (n=10) Elispot assays. Circulating DC subset numbers and their maturation status determined by CCR2, CCR5, CCR7, and CD83 expression were measured by flow cytometry (n=12).
  
  
  RESULTS
  The number of donor, third-party, and tetanus toxoid-reactive interferon-gamma and granzyme-B producing cells was not affected after withdrawal of immunosuppression. Discontinuation of AZA or MMF resulted in significant increased numbers of third-party (P=0.003) and tetanus toxoid-reactive (P=0.008) IL-10 producing cells, and a trend in higher numbers of donor-reactive IL-10 producing cells (P=0.06). No effect was found on the number of circulating DC subsets, but DC was shifted toward a more mature phenotype.
  
  
  CONCLUSIONS
  In HLA-identical LR renal transplant recipients, therapy with AZA and MMF suppress the IL-10 production and the maturation of DC. This suggests that these immunosuppressants may hinder suppression of immune responses in general, including allogeneic responses.
authors.affiliation: Department of Internal Medicine-Transplantation, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Jeroen H
authors.initials: JH
authors.lastname: Gerrits
authors.forename: Jacqueline
authors.initials: J
authors.lastname: van de Wetering
authors.forename: Willem
authors.initials: W
authors.lastname: Weimar
authors.forename: Nicole M
authors.initials: NM
authors.lastname: van Besouw
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use; D002648:Child; D004334:Drug Administration Schedule; D005190:Family; D005260:Female; D053804:Granzymes / Q000276:immunology; D006680:HLA Antigens / Q000032:analysis / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011239:Prednisolone / Q000627:therapeutic use*; D012086:Reoperation; D013601:T-Lymphocytes / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D007166:Immunosuppressive Agents; D013745:Tetanus Toxoid; D016753:Interleukin-10; D011239:Prednisolone; D053804:Granzymes; D009173:Mycophenolic Acid; D001379:Azathioprine