title: Role of thymus in operational tolerance induction in limb allograft transplant model.
abstract: BACKGROUND
  In this study, we evaluated the role of host thymus in tolerance induction in composite tissue allografts (CTA) across major histocompatibility complex (MHC) barrier during a 7-day alphabeta- T-cell receptor (TCR)/ cyclosporine A (CsA) protocol.
  
  
  METHODS
  A total of 62 limb allograft transplants were studied. Euthymic (group A) and thymectomized (group B) Lewis recipients (LEW, RT1(1)) received vascularized hind-limb allografts from hybrid Lewis x Brown-Norway (F1), (LBN, RT1(1+n)) donors. Mixed lymphocyte reaction (MLR) and skin grafting assessed donor-specific tolerance in vitro and in vivo, respectively. Flow cytometry determined the efficacy of immunosuppressive protocols and the presence of donor-specific chimerism. Immunocytochemistry revealed the presence of donor-specific cells in the lymphoid organs of recipients.
  
  
  RESULTS
  Isograft transplants survived indefinitely. For thymectomized rats, the median survival time (MST) of limb allograft in non-treated recipients was 7 days; monotherapy with alphabeta-TCR extended MST to 16 days, and CsA therapy extended it to 30 days. Using the alphabeta-TCR/CsA protocol, the MST of allografts was 51 days. For euthymic rats, the MST of limb allograft in non-treated recipients was 7 days; monotherapy with alphabeta-TCR or CsA extended MST to 13 or 22 days, respectively. Treatment with alphabeta-TCR/CsA resulted in indefinite allografts survival (MST=370 days). MLR and skin grafting confirmed donor-specific tolerance in euthymic recipients. Flow cytometry showed stable chimerism in the euthymic rats and transient chimerism in thymectomized limb recipients. Immunoperoxidase staining revealed the persistence of donor-derived cells in the lymphoid tissues of euthymic recipients.
  
  
  CONCLUSIONS
  We found that the presence of thymus was imperative for the induction of donor-specific tolerance in rat hind-limb composite tissue allografts using a alphabeta-TCR/CsA protocol.
authors.affiliation: Department of Plastic Surgery, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. siemiom@ccf.org
authors.forename: Maria
authors.initials: M
authors.lastname: Siemionow
authors.forename: Dariusz
authors.initials: D
authors.lastname: Izycki
authors.forename: Kagan
authors.initials: K
authors.lastname: Ozer
authors.forename: Selahattin
authors.initials: S
authors.lastname: Ozmen
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Klimczak
mesh_terms: D000818:Animals; D046528:Chimerism; D016572:Cyclosporine / Q000627:therapeutic use; D005434:Flow Cytometry; D006614:Hindlimb / Q000473:pathology / Q000503:physiopathology / Q000637:transplantation*; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007959:Lymphocyte Culture Test, Mixed; D008221:Lymphoid Tissue / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000627:therapeutic use; D015996:Survival Rate; D013934:Thymectomy; D013950:Thymus Gland / Q000276:immunology* / Q000601:surgery; D013997:Time Factors; D023001:Transplantation Tolerance / Q000187:drug effects / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology* / Q000473:pathology
chemical_list: D007166:Immunosuppressive Agents; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016572:Cyclosporine