title: FTY720 reduces T-cell recruitment into murine intestinal allograft and prevents activation of graft-infiltrating cells.
abstract: BACKGROUND
  Effective immunosuppression is a critical determinant of graft survival in small-bowel transplantation (SBTx). The present study was designed to determine the potency of FTY720, a newly synthesized immunosuppressant, in rat SBTx and examine the phenotype of graft-infiltrating cells to evaluate its effect on intestinal allografts.
  
  
  METHODS
  A segment of intestine of Dark Agouti rats was transplanted heterotopically into Lewis rats. The recipients were treated with or without oral FTY720 at a dose of 1 mg/kg per day. Six days after surgery, peripheral blood lymphocytes and lymphocytes from the mesenteric lymph nodes, Peyer's patches, intraepithelial site, and lamina propria of the intestinal allograft were isolated. After the number of lymphocytes in each site was counted, the lymphocyte subpopulations in the intestinal allograft were evaluated by means of a FACScan flow cytometer using several monoclonal antibodies.
  
  
  RESULTS
  FTY720 treatment significantly prolonged recipient survival and strongly inhibited rejection histologically in comparison with control rats. FTY720 immunosuppression resulted in a marked reduction of lymphocyte number in the graft epithelium and lamina propria and the proportion of CD8+ and CD25+ cells. FTY720 also significantly decreased T-cell receptors and increased B cells in the graft Peyer's patches.
  
  
  CONCLUSIONS
  FTY720 promoted long-term SBTx recipient survival and maintained the architecture of intestinal allografts. FTY720 immunosuppression may be associated with a reduction of T-cell recruitment subsequent to the redistribution of lymphocyte subpopulations to control the proliferation and activation of graft-infiltrating cells in intestinal allografts.
authors.affiliation: Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kimura
authors.forename: Toshimichi
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakai
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Azuma
authors.forename: Noriaki
authors.initials: N
authors.lastname: Usui
authors.forename: Takashi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Akira
authors.initials: A
authors.lastname: Okada
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007421:Intestine, Small / Q000473:pathology* / Q000637:transplantation*; D008297:Male; D011409:Propylene Glycols / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D013110:Sphingosine / Q000031:analogs & derivatives; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine