Thymectomy impairs but does not uniformly abrogate long-term acceptance of semi-identical liver allograft in inbred miniature Swine temporarily treated with FK506.

Abstract:

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.

journal_name

Transplantation

journal_title

Transplantation

authors

Uryuhara K,Ambiru S,Dehoux JP,Oike F,Talpe S,Gianello P

doi

10.1097/01.tp.0000121762.47432.15

subject

Has Abstract

pub_date

2004-04-27 00:00:00

pages

1172-80

issue

8

eissn

0041-1337

issn

1534-6080

pii

00007890-200404270-00008

journal_volume

77

pub_type

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