Indirect recognition of MHC class I allopeptides accelerates lung allograft rejection in miniature swine.
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.
Shoji
Tsuyoshi
T
Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Wain
John C
JC
Houser
Stuart L
SL
Benjamin
Louis C
LC
Johnston
Douglas R
DR
Hoerbelt
Ruediger
R
Hasse
Rebecca S
RS
Lee
Richard S
RS
Muniappan
Ashok
A
Guenther
Dax A
DA
Bravard
Marjory A
MA
Ledgerwood
Levi G
LG
Sachs
David H
DH
Sayegh
Mohamed H
MH
Madsen
Joren C
JC
Allan
James S
JS
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
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007518:Isoantibodies; D007519:Isoantigens