Thymectomy impairs but does not uniformly abrogate long-term acceptance of semi-identical liver allograft in inbred miniature Swine temporarily treated with FK506.
BACKGROUND
Long-term acceptance of semi-identical orthotopic liver transplants (OLTs) in inbred swine is induced by a 12-day course of FK506. To study whether acceptance is attributable to central or peripheral immune mechanisms, the effect of complete thymectomy was determined.


METHODS
Total thymectomy was performed in 15 swine 3 to 4 weeks before OLT. Twelve of these animals received a 12-day course of FK506 after OLT, and three animals did not receive immunosuppression. Five additional nonthymectomized pigs received OLT and a FK506 regimen. Graft survival, liver function, histology, and cellular and humoral responses were assessed.


RESULTS
Nonthymectomized, FK506-treated animals uniformly showed long-term acceptance of OLT and developed stable donor unresponsiveness. Of the 12 thymectomized, FK506-treated pigs, seven died of non-immunologic causes within 3 postoperative months, and five maintained their OLT for more than 6 months (range 180-450 days). Among these survivors, two developed a complete anti-donor response (mixed lymphocyte reaction [MLR], cell-mediated lymphocytotoxicity [CML], and immunoglobulin [IgG] antibodies) and eventually rejected their OLT at postoperative day 180. The three remaining pigs kept their liver allografts up to 450 days and developed a donor-specific unresponsiveness (a transient anti-donor MLR was observed during the follow-up but never an anti-donor CML or IgG antibodies). All three thymectomized, untreated animals rejected their allografts acutely and displayed a complete anti-donor response (MLR, CML, and IgG antibodies).


CONCLUSIONS
Complete thymectomy before OLT impaired but did not uniformly abrogate long-term acceptance of semi-identical OLT, suggesting that peripheral immune mechanisms may be sufficient to induce long-term acceptance of liver allografts in some recipients.
Uryuhara
Kenji
K
Laboratory of Experimental Surgery, Faculté de Médecine, Université Catholique de Louvain, Brussels, Belgium.
Ambiru
Satoshi
S
Dehoux
Jean-Paul
JP
Oike
Fumitaka
F
Talpe
Stephanie
S
Gianello
Pierre
P
D000818:Animals; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007178:Inbreeding; D007518:Isoantibodies / Q000096:biosynthesis; D016031:Liver Transplantation / Q000276:immunology* / Q000473:pathology / Q000502:physiology; D007959:Lymphocyte Culture Test, Mixed; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013552:Swine; D013556:Swine, Miniature; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology*; D013934:Thymectomy; D023001:Transplantation Tolerance / Q000187:drug effects / Q000276:immunology; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D007518:Isoantibodies; D016559:Tacrolimus