Indirect Recognition of MHC Class I Allopeptides Accelerates Lung Allograft Rejection in Miniature Swine |
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Authors: | Tsuyoshi Shoji John C Wain Stuart L Houser Louis C Benjamin Douglas R Johnston Ruediger Hoerbelt Rebecca S Hasse Richard S Lee Ashok Muniappan Dax A Guenther Marjory A Bravard Levi G Ledgerwood David H Sachs Mohamed H Sayegh Joren C Madsen James S Allan |
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Institution: | Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. |
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Abstract: | The role of indirect allorecognition in graft rejection is examined in two experiments using a swine lung transplantation model. First, two swine received class I mismatched grafts without immunosuppression; another two recipients were treated postoperatively with cyclosporine (CsA). These swine exhibited acute and chronic rejection, respectively. All four recipients developed T-cell reactivity to donor-derived class I major histocompatibility complex (MHC) peptides. Second, six swine were immunized with synthetic donor-derived class I allopeptides prior to transplantation. Control groups consisted of nonimmunized recipients (n = 6) and recipients immunized with an irrelevant peptide (n = 3). These recipients all received a 12-day course of post-operative CsA. Swine immunized with allopeptides exhibited accelerated graft rejection, as compared to both control groups (p < 0.01 and p = 0.03, respectively). Within the experimental group, the dominant histologic finding was acute rejection (AR). Obliterative bronchiolitis (OB) was seen in the graft with the longest survival. Both control groups showed a lesser degree of AR, with four out of six nonimmunized swine ultimately developing OB. These studies suggest that indirect allorecognition is operative during lung allograft rejection, and that pre-transplant sensitization to donor-derived MHC allopeptides can accelerate graft rejection. |
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Keywords: | Indirect allorecognition Lung MHC peptides rejection swine transplantation |
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