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Indirect Recognition of MHC Class I Allopeptides Accelerates Lung Allograft Rejection in Miniature Swine
Author(s) -
Shoji Tsuyoshi,
Wain John C.,
Houser Stuart L.,
Benjamin Louis C.,
Johnston Douglas R.,
Hoerbelt Ruediger,
Hasse Rebecca S.,
Lee Richard S.,
Muniappan Ashok,
Guenther Dax A.,
Bravard Marjory A.,
Ledgerwood Levi G.,
Sachs David H.,
Sayegh Mohamed H.,
Madsen Joren C.,
Allan James S.
Publication year - 2005
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2005.00925.x
Subject(s) - medicine , lung , major histocompatibility complex , miniature swine , immunology , immune system
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.