title: Indirect recognition of MHC class I allopeptides accelerates lung allograft rejection in miniature swine.
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.
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shoji
authors.forename: John C
authors.initials: JC
authors.lastname: Wain
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Houser
authors.forename: Louis C
authors.initials: LC
authors.lastname: Benjamin
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Johnston
authors.forename: Ruediger
authors.initials: R
authors.lastname: Hoerbelt
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Hasse
authors.forename: Richard S
authors.initials: RS
authors.lastname: Lee
authors.forename: Ashok
authors.initials: A
authors.lastname: Muniappan
authors.forename: Dax A
authors.initials: DA
authors.lastname: Guenther
authors.forename: Marjory A
authors.initials: MA
authors.lastname: Bravard
authors.forename: Levi G
authors.initials: LG
authors.lastname: Ledgerwood
authors.forename: David H
authors.initials: DH
authors.lastname: Sachs
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Sayegh
authors.forename: Joren C
authors.initials: JC
authors.lastname: Madsen
authors.forename: James S
authors.initials: JS
authors.lastname: Allan
mesh_terms: D000208:Acute Disease; D000818:Animals; D049109:Cell Proliferation; D002908:Chronic Disease; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007114:Immunization; D007518:Isoantibodies / Q000096:biosynthesis; D007519:Isoantigens / Q000276:immunology*; D008168:Lung / Q000473:pathology; D016040:Lung Transplantation / Q000276:immunology*; D013552:Swine; D013556:Swine, Miniature; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D013997:Time Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007518:Isoantibodies; D007519:Isoantigens