title: Induction of tolerance to hind limb allografts in rats receiving cyclosporine A and antilymphocyte serum: effect of duration of the treatment.
abstract: BACKGROUND
  This study assessed the ability of antilymphocyte serum (ALS) and cyclosporine A (CsA) to induce tolerance for hind limb composite tissue allograft in rats without chronic immunosuppression.
  
  
  METHODS
  Hind limb transplantations were performed in Lewis-Brown-Norway (LBN, RT1(1+n)) and Lewis (LEW, RT1(1)) rats. Treatment consisted of ALS only (0.4 mL/kg), CsA only (16 mg/kg), and a combination of CsA and ALS, and it was administered 12 hr before surgery at three different intervals (7, 14, and 21 days). Long-term survivors were tested for tolerance by standard skin grafting from the recipient (LEW), the donor (LBN), and the third party (ACI, RT1 ) 60 days after cessation of the treatment and by mixed lymphocyte reaction at 100 days. T-cell lines were analyzed with flow cytometry.
  
  
  RESULTS
  Single use of ALS in all treatment intervals did not prolong allograft survival. Single use of CsA extended survival up to 23 days in the 21-day protocol group. CsA and ALS caused indefinite survival in two of six rats in the 14-day protocol and in all six rats in the 21-day protocol (>420 days). The six long-term survivors in the 21-day protocol accepted the skin grafts from the donor (LBN) and the recipient (LEW) and rejected third-party grafts (ACI). Tolerant animals showed a donor-specific hematopoietic chimerism of 35% to 42% in the peripheral blood. Mixed lymphocyte reaction assay demonstrated tolerance to the host and donor alloantigens and increased response to the third party.
  
  
  CONCLUSIONS
  Administration of CsA and ALS for 21 days induced donor-specific tolerance in the recipients of the rat hind limb composite tissue allografts. The mechanism of tolerance should be investigated further.
authors.affiliation: Department of Plastic Surgery, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: Kagan
authors.initials: K
authors.lastname: Ozer
authors.forename: Ramadan
authors.initials: R
authors.lastname: Oke
authors.forename: Raffi
authors.initials: R
authors.lastname: Gurunluoglu
authors.forename: Maciej
authors.initials: M
authors.lastname: Zielinski
authors.forename: Dariusz
authors.initials: D
authors.lastname: Izycki
authors.forename: Rita
authors.initials: R
authors.lastname: Prajapati
authors.forename: Maria
authors.initials: M
authors.lastname: Siemionow
mesh_terms: D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D016026:Bone Marrow Transplantation; D016572:Cyclosporine / Q000008:administration & dosage*; D005434:Flow Cytometry; D006085:Graft Survival; D006614:Hindlimb / Q000637:transplantation*; D007108:Immune Tolerance; D016030:Kidney Transplantation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
chemical_list: D000961:Antilymphocyte Serum; D016572:Cyclosporine