title: Effects of FTY720 on peripheral blood lymphocytes and graft infiltrating cells in a rat model of chronic renal allograft rejection.
abstract: OBJECTIVE
  Chronic renal allograft loss is still an unsolved problem in kidney transplantation. We evaluated the impact of FTY720, a S1P receptor agonist, known to deplete lymphocytes from the peripheral blood by sequestering them into lymph nodes and Peyer's patches, on blood lymphocytes and graft infiltrating cells in a rat model of chronic real allograft rejection.
  
  
  METHODS
  LEW rats served as recipients for LEW.1U7B kidney grafts. All animals were treated with CsA (5mg/kg) for 10 days after renal transplantation and monitored for kidney function, peripheral blood lymphocytes and graft infiltrating cells. In the intervention group (n=7) FTY720 therapy was started 7 weeks post-KTx in a dose of 0.5 mg/kg p. o. three times a week.
  
  
  RESULTS
  In the control group the survival of the rats was 9, 11, 18 and 4 × 24 weeks, in the intervention group 2 × 8, 9, 2 × 11, 18 and 20 weeks. While in the intervention group the number of T- and B-lymphocytes in the peripheral blood was successfully reduced during FTY720 treatment, both groups showed significant amounts of T- and B-lymphocytes in the kidney grafts. Animals in both groups developed donor specific antibodies, extensive albuminuria and severe chronic changes in the grafts.
  
  
  CONCLUSIONS
  FTY720 was highly effective to reduce T- and B-lymphocytes in the peripheral blood, but not effective in clearing their infiltration in the graft. Graft survival was not prolonged by FTY720 treatment starting late after kidney transplantation.
authors.affiliation: Klinik fuer Hepatobiliäre Chirurgie und Transplantationschirurgie, UKE, Martinistr. 52, 20246 Hamburg, Germany. Electronic address: martina.koch@uke.de.
authors.forename: Martina
authors.initials: M
authors.lastname: Koch
authors.affiliation: Klinik fuer Allgemein-, Viszeral- und Transplantationschirurgie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Poehnert
authors.affiliation: Klinik fuer Hepatobiliäre Chirurgie und Transplantationschirurgie, UKE, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Nashan
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology*; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D007111:Immunity, Cellular / Q000187:drug effects*; D056724:Immunity, Humoral / Q000187:drug effects*; D016030:Kidney Transplantation; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D000068876:Fingolimod Hydrochloride
keywords: Chronic rejection; FTY720; Graft infiltrating cells; Kidney transplantation; Rat model