title: Validation of Donor-Specific Tolerance of Intestinal Transplant by a Secondary Heart Transplantation Model.
abstract: OBJECTIVE
  It is well accepted that survival after a second organ transplant without immunosuppressive agents indicates tolerance for the first transplant. To validate donor-specific tolerance, we established a rat model with a secondary heart transplant after intestinal transplant, which has so far not been described in the literature.
  
  
  METHODS
  We transplanted intestine from Fischer F344 rats to Lewis rats orthotopically. Lewis rats received tacrolimus pretreatment before transplant and a 14-day course of rapamycin 1 month after transplant. At 120 days after primary intestinal transplant, hearts from 6 F344 rats (group A) or 6 Brown Norway rats (group B) were transplanted to Lewis rats that had survived intestinal transplant and without additional immunosuppressive agents. We analyzed survival data, histologic changes, cells positive for the ED1 macrophage marker in transplanted hearts, and 3 lymphocyte levels in both groups.
  
  
  RESULTS
  Thirty days after secondary heart transplant, group A hearts were continuously beating; however, group B hearts stopped beating at around 10 days after transplant (8.5 ± 1.5 d; P < .05). Our histologic study showed that both groups had muscle damage and cellular infiltration in hearts that were distinctly different from normal hearts, with ED1-positive cells counted in both groups (85 ± 16 in group A, 116 ± 28 in group B; P > .05). Fluorescence-activated cell sorting showed that CD4/CD25-positive regulatory T cell, CTLA4/CD4/CD25-positive regulatory T cell, and Natural killer T-cell levels were significantly higher level in group A versus B (P < .05).
  
  
  CONCLUSIONS
  The donor-specific tolerance that we observed was possibly a state of "clinical tolerance" rather than "immunologic tolerance." Our rat model is a feasible and reliable model to study donor-specific tolerance. The higher levels of lymphocytic T cells shown in intestinal transplant recipients were associated with longer allograft survival, possibly contributing to donor-specific tolerance.
authors.affiliation: Department of Cardiac Surgery, Beijing Children's Hospital Affiliated to Capital Medical University, Beijing, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Pengcheng
authors.forename: Li
authors.initials: L
authors.lastname: Xiaosong
authors.forename: Li
authors.initials: L
authors.lastname: Xiaofeng
authors.forename: Li
authors.initials: L
authors.lastname: Zhongzhi
mesh_terms: D064591:Allografts; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007422:Intestines / Q000276:immunology / Q000637:transplantation*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D023421:Models, Animal; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D020123:Sirolimus / Q000008:administration & dosage; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D016559:Tacrolimus / Q000008:administration & dosage; D013997:Time Factors; D023001:Transplantation Tolerance / Q000187:drug effects
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus