title: Graft-specific immune cells communicate inflammatory immune responses after brain death.
abstract: BACKGROUND
  Donor brain death (BD) triggers inflammatory graft activation that leads to impaired graft quality and outcome. We used a mouse BD model to investigate graft inflammation in cardiac transplants from immune-competent and immune-deficient donor animals. Effects of donor T-cell depletion were tested in an additional group of cardiac transplant recipients.
  
  
  METHODS
  We analyzed systemic and graft-specific inflammatory activation after BD in donors and in syngeneic recipients of hearts retrieved from BD donors. To dissect the role of donor-specific immune cells in communicating BD-triggered inflammation, immune-deficient T-cell-, B-cell-, and natural killer cell-deficient Rag2/double knockout mice and naïve C57BL6 treated with anti-thymocyte globulin (Thymoglobulin; Genzyme Transplant, Cambridge, MA) were observed.
  
  
  RESULTS
  Donor BD boosted lymphocyte activation in donors and recipients of syngeneic BD grafts. Lymphocyte activation was mitigated in recipients of immune-deficient and Thymoglobulin-treated BD donor grafts. Likewise, systemic and intra-graft levels of inflammatory cytokines interleukin -1, interleukin-6, interferon-γ, and tumor necrosis factor-α were significantly reduced in immune-deficient and anti-thymocyte globulin-treated recipients. Dense lymphocyte infiltrates were detected in the hearts from untreated BD donors; in contrast, the hearts from donors treated with Thymoglobulin demonstrated a preserved structure with minimal infiltrates comparable with naïve controls.
  
  
  CONCLUSIONS
  BD triggers inflammatory graft activation communicated through intra-graft immune cells. Donor treatment with Thymoglobulin prevented inflammatory immune activation and improved graft quality to levels comparable to living donor organs.
authors.affiliation: Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Floerchinger
authors.forename: Xupeng
authors.initials: X
authors.lastname: Ge
authors.forename: Ying-Lung
authors.initials: YL
authors.lastname: Lee
authors.forename: Anke
authors.initials: A
authors.lastname: Jurisch
authors.forename: Robert F
authors.initials: RF
authors.lastname: Padera
authors.forename: Christof
authors.initials: C
authors.lastname: Schmid
authors.forename: Stefan G
authors.initials: SG
authors.lastname: Tullius
mesh_terms: D000818:Animals; D000961:Antilymphocyte Serum / Q000494:pharmacology; D001926:Brain Death / Q000276:immunology*; D002450:Cell Communication / Q000502:physiology*; D005434:Flow Cytometry; D016027:Heart Transplantation / Q000276:immunology*; D007136:Immunoglobulins / Q000502:physiology; D007249:Inflammation / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000502:physiology*; D014019:Tissue Donors
chemical_list: D000961:Antilymphocyte Serum; D007136:Immunoglobulins; C512542:thymoglobulin