Thymic transplantation in miniature swine: III. Induction of tolerance by transplantation of composite thymokidneys across fully major histocompatibility complex-mismatched barriers.
BACKGROUND
This study determines whether composite thymokidney (TK) grafts, created by implantation of autologous thymic tissue beneath the donor's renal capsule before transplantation, could induce allogeneic transplantation tolerance across two-haplotype fully major histocompatibility complex (MHC)- mismatched barriers in juvenile MGH-miniature swine.


METHODS
TK grafts were prepared by implanting autologous thymic tissue under the renal capsule of donor animals 2 to 3 months before transplantation. Four recipients were treated with a T-cell-depleting immunotoxin and received fully MHC-mismatched TK grafts plus a 12-day course of cyclosporine A (CsA). Control animals were treated with CsA alone or both CsA and immunotoxin, but with a normal kidney or a kidney implanted with autologous lymph node rather than thymus. Renal graft function was assessed by plasma creatinine levels and histologic analyses. Immunologic status was monitored by cell-mediated lympholysis assays.


RESULTS
All four recipients of fully MHC-mismatched TK transplants treated with immunotoxin and a 12-day course of CsA accepted their composite renal allografts long-term. All control recipients receiving a TK and CsA alone, a normal kidney or a composite kidney containing lymph node tissue acutely rejected their grafts.


CONCLUSIONS
To our knowledge, this is the first demonstration that functional vascularized thymic grafts can induce transplantation tolerance across fully MHC-mismatched barriers in a large animal model.
Yamada
Kazuhiko
K
Transplantation Biology Research Center, Massachusetts General Hospital, Boston, Massachusetts 02129, USA.
Vagefi
Parsia A
PA
Utsugi
Ryu
R
Kitamura
Hiroshi
H
Barth
Rolf N
RN
LaMattina
John C
JC
Sachs
David H
DH
D000818:Animals; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000494:pharmacology; D006648:Histocompatibility / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D000922:Immunotoxins / Q000494:pharmacology; D016030:Kidney Transplantation; D008285:Major Histocompatibility Complex / Q000276:immunology; D013556:Swine, Miniature; D013950:Thymus Gland / Q000637:transplantation*; D014184:Transplantation, Homologous
D000922:Immunotoxins; D016572:Cyclosporine; D003404:Creatinine