title: Regulatory T cells in kidney transplant recipients: the effect of induction immunosuppression therapy.
abstract: BACKGROUND
  Regulatory T cells have been suggested to down-regulate the alloimmune response. The aim of this prospective open study was to evaluate the effects of different inductive agents on peripheral blood regulatory T cells in kidney transplant patients and to analyse their association with short-term graft outcome.
  
  
  METHODS
  Regulatory and effector T cell numbers in peripheral blood were determined by flow cytometry in 71 prospectively followed kidney transplant recipients at postoperative day 0, 7, 14, 21, 28, 60 and 90. Patients were treated with a calcineurin inhibitor-based triple immunosuppression with polyclonal rabbit anti-thymocyte globulin (rATG, n = 28), basiliximab, the anti-CD25 monoclonal antibody (n = 18) or without induction (controls, n = 25). Flow cytometry data were correlated to rejection incidence.
  
  
  RESULTS
  Compared to controls, CD4(+)CD25(+)FoxP3(+) regulatory T-cell expansion among CD4(+) T cells was noticed in the rATG group at all post-transplant time-points by Day 14 (P < 0.001). A significant decrease in Treg frequency (P < 0.001) and concurrently a transient increase of CD4(+)CD25(low/-)FoxP3(+) population were observed in basiliximab-treated patients 7-60 days post-transplantation. Biopsy-proven acute rejection occurred in 16.7% of controls, 10.7% of the rATG group and in 11.1% of the basiliximab group. Higher CD4(+)FoxP3(+)/CD8(+)CD45RA(+)CD62L(-) ratios were observed repeatedly in those patients after basiliximab induction who were rejection free (P < 0.01).
  
  
  CONCLUSIONS
  In this study, the rATG induction therapy was associated with an expansion of regulatory cells. Sustained high CD4(+)FoxP3(+)/Teff ratios were associated with the absence of rejection after basiliximab induction.
authors.affiliation: Transplant Laboratory, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Krystufkova
authors.forename: Alena
authors.initials: A
authors.lastname: Sekerkova
authors.forename: Ilja
authors.initials: I
authors.lastname: Striz
authors.forename: Irena
authors.initials: I
authors.lastname: Brabcova
authors.forename: Eva
authors.initials: E
authors.lastname: Girmanova
authors.forename: Ondrej
authors.initials: O
authors.lastname: Viklicky
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D000077552:Basiliximab; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; C508017:IL2RA protein, human; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab