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Tacrolimus pretreatment attenuates preexisting xenospecific immunity and abrogates hyperacute rejection in a presensitized hamster to rat liver transplant model

Tsugita, M and Valdivia, LA and Rao, AS and Pan, F and Celli, S and Demetris, AJ and Fung, JJ and Starzl, TE (1996) Tacrolimus pretreatment attenuates preexisting xenospecific immunity and abrogates hyperacute rejection in a presensitized hamster to rat liver transplant model. Transplantation, 61 (12). 1730 - 1735. ISSN 0041-1337

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Abstract

In the hamster to rat liver transplant model, we determined the efficacy of tacrolimus in attenuating natural xenospecific humoral immunity and in abrogating the hyperacute liver rejection that is produced by presensitizing the Lewis rat recipient. Hamster livers, transplanted orthotopically into naive rats (controls), were rejected with animal death after 6.4±0.5 (SD) days. The infusion on (day -6) of 1.5 x 107 hamster hepatocytes, or of 1.5 x 108 nonparenchymal cells (NPC), resulted in hyperacute rejection and death in ≤1.9 days. However, when the rats were pretreated with 1 mg/kg/day tacrolimus from days -6 to -1, survival of non-presensitized animals was prolonged to 25±20 days and that of recipients presensitized with hamster hepatocytes to 36±16 days or with NPC to 32±1.7 days. The tacrolimus pretreatment significantly reduced the hamster-specific complement-dependent cytotoxic antibodies response directed to liver NPC but not to lymph node cell targets. These observations suggest that the prolongation of survival by appropriately timed treatment with this T cell directed drug model is caused by the inhibition of humoral as well as cellular xenograft rejection.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Tsugita, M
Valdivia, LA
Rao, AS
Pan, F
Celli, S
Demetris, AJ
Fung, JJ
Starzl, TEtes11@pitt.eduTES11
Centers: Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute
Date: 27 June 1996
Date Type: Publication
Journal or Publication Title: Transplantation
Volume: 61
Number: 12
Page Range: 1730 - 1735
DOI or Unique Handle: 10.1097/00007890-199606270-00012
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0041-1337
Other ID: uls-drl:31735062133271, Starzl CV No. 1863
Date Deposited: 08 Apr 2010 17:31
Last Modified: 13 Jun 2021 02:55
URI: http://d-scholarship.pitt.edu/id/eprint/5249

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