Graft-specific immune cells communicate inflammatory immune responses after brain death

Floerchinger, Bernhard and Ge, Xupeng and Lee, Ying-Lung and Jurisch, Anke and Padera, Robert F. and Schmid, Christof and Tullius, Stefan G. (2012) Graft-specific immune cells communicate inflammatory immune responses after brain death. JOURNAL OF HEART AND LUNG TRANSPLANTATION, 31 (12). pp. 1293-1300. ISSN 1053-2498,

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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 naive 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-gamma, and tumor necrosis factor-a 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 naive controls. CONCLUSION: BD triggers inflammatory graft activation communicated through ultra-graft immune cells. Donor treatment with Thymoglobulin prevented inflammatory immune activation and improved graft quality to levels comparable to living donor organs. J Heart Lung Transplant 2012; 31: 1293-300 (C) 2012 International Society for Heart and Lung Transplantation. All rights reserved.

Item Type: Article
Uncontrolled Keywords: RANDOMIZED CONTROLLED-TRIAL; RAT RENAL ISOGRAFTS; TRANSPLANT RECIPIENTS; REDUCES INFLAMMATION; DONOR PRETREATMENT; ACUTE REJECTION; ACTIVATION; MODEL; INDUCTION; THERAPY; donor brain death; inflammatory graft activation; immune cells; Thymoglobulin
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Herz-, Thorax- und herznahe Gefäßchirurgie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 04 May 2020 05:15
Last Modified: 04 May 2020 05:15
URI: https://pred.uni-regensburg.de/id/eprint/17654

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