title: Immunological monitoring of renal transplant recipients to predict acute allograft rejection following the discontinuation of tacrolimus.
abstract: BACKGROUND
  Transplant patients would benefit from reduction of immunosuppression providing that graft rejection is prevented. We have evaluated a number of immunological markers in blood of patients in whom tacrolimus was withdrawn after renal transplantation. The alloreactive precursor frequency of CD4+ and CD8+ T cells, the frequency of T cell subsets and the functional capacity of CD4+CD25+FoxP3+ regulatory T cells (Treg) were analyzed before transplantation and before tacrolimus reduction. In a case-control design, the results were compared between patients with (n = 15) and without (n = 28) acute rejection after tacrolimus withdrawal.
  
  
  RESULTS
  Prior to tacrolimus reduction, the ratio between memory CD8+ T cells and Treg was higher in rejectors compared to non-rejectors. Rejectors also had a higher ratio between memory CD4+ T cells and Treg, and ratios <20 were only observed in non-rejectors. Between the time of transplantation and the start of tacrolimus withdrawal, an increase in naive T cell frequencies and a reciprocal decrease of effector T cell percentages was observed in rejectors. The proportion of Treg within the CD4+ T cells decreased after transplantation, but anti-donor regulatory capacity of Treg remained unaltered in rejectors and non-rejectors.
  
  
  CONCLUSIONS
  Immunological monitoring revealed an association between acute rejection following the withdrawal of tacrolimus and 1) the ratio of memory T cells and Treg prior to the start of tacrolimus reduction, and 2) changes in the distribution of naive, effector and memory T cells over time. Combination of these two biomarkers allowed highly specific identification of patients in whom immunosuppression could be safely reduced.
authors.affiliation: Department of Blood Transfusion and Transplantation Immunology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Ellen
authors.initials: E
authors.lastname: Kreijveld
authors.forename: Hans J P M
authors.initials: HJ
authors.lastname: Koenen
authors.forename: Bram
authors.initials: B
authors.lastname: van Cranenbroek
authors.forename: Esther
authors.initials: E
authors.lastname: van Rijssen
authors.forename: Irma
authors.initials: I
authors.lastname: Joosten
authors.forename: Luuk B
authors.initials: LB
authors.lastname: Hilbrands
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D006084:Graft Rejection / Q000175:diagnosis*; D006801:Humans; D007107:Immune System; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic / Q000379:methods*; D016559:Tacrolimus / Q000627:therapeutic use*; D014184:Transplantation, Homologous
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D016559:Tacrolimus