title: Role of the thymus in transplantation tolerance in miniature Swine: IV. The thymus is required during the induction phase, but not the maintenance phase, of renal allograft tolerance.
abstract: BACKGROUND
  The authors' laboratory previously demonstrated that long-term tolerance to class I-disparate renal allografts in miniature swine can be induced by a short course of cyclosporine A (CsA), and that this stable tolerance is dependent on the presence of an intact thymus. In the present study, the authors have examined the requirement for a thymus during the pretransplant, induction, and maintenance phases of tolerance.
  
  
  METHODS
  Twenty-two miniature swine underwent class I major histocompatibility complex-mismatched renal transplantation, with a 12-day course of CsA. Thymectomies were performed on days -21, 0, +8, +21, and greater than or equal to +42, in relation to the day of transplantation. Historical controls consisted of euthymic and sham-thymectomized recipients.
  
  
  RESULTS
  Euthymic, sham-thymectomized, and day-greater than or equal to +42 thymectomized recipients demonstrated stable renal function and minimal anti-donor cytotoxic T-lymphocyte (CTL) responses. In contrast, day -21 and day 0 thymectomized recipients demonstrated allograft dysfunction, marked cellular infiltrates, with severe vasculitis and glomerular changes, and strong anti-donor CTL responses. Animals thymectomized on days +8 and +21 did not undergo severe rejection, but likewise did not demonstrate a stable clinical course.
  
  
  CONCLUSIONS
  These data indicate that the requirement for thymic function in the induction of rapid and stable tolerance is greatest during the first 8 days and then diminishes over the next 2 weeks posttransplant. Failure of thymectomy to affect the course of tolerance after day +21 suggests that thymic function is not required for the maintenance of tolerance. Understanding the role of the thymus in establishing tolerance may permit the development of tolerance induction strategies, especially for pediatric transplant recipients.
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital-Harvard Medical School, Boston, MA 02129, USA.
authors.forename: Parsia A
authors.initials: PA
authors.lastname: Vagefi
authors.forename: Francesco L
authors.initials: FL
authors.lastname: Ierino
authors.forename: Pierre R
authors.initials: PR
authors.lastname: Gianello
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.forename: Chisako
authors.initials: C
authors.lastname: Kamano
authors.forename: David H
authors.initials: DH
authors.lastname: Sachs
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamada
mesh_terms: D000818:Animals; D006084:Graft Rejection; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007108:Immune Tolerance; D016030:Kidney Transplantation / Q000276:immunology*; D013552:Swine; D013556:Swine, Miniature; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013934:Thymectomy; D013950:Thymus Gland / Q000502:physiology*; D014184:Transplantation, Homologous
chemical_list: D015395:Histocompatibility Antigens Class I