Abrogation of chronic rejection in a murine model of aortic allotransplantation by prior induction of donor-specific tolerance

Subbotin, V and Sun, H and Aitouche, A and Valdivia, LA and Fung, JJ and Starzl, TE and Rao, AS (1997) Abrogation of chronic rejection in a murine model of aortic allotransplantation by prior induction of donor-specific tolerance. Transplantation, 64 (5). 690 - 695. ISSN 0041-1337

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Abstract

Aortic allotransplantation in mice has been well established as a model of choice to study the evolvement of chronic rejection, the etiopathology of which is believed to be that of immune origin. This has prompted the postulation that prior induction of donor-specific tolerance would attenuate or abrogate the underlying events that culminate in posttransplant arteriosclerosis. To study the effects of donor-specific tolerance on chronic rejection, we performed orthotopic liver transplantation without immunosuppression in mice 30 days before aortic allotransplantation across C57Bl/10J (H2b)→C3H (H2(k)) strain combinations (group III). Aortic allografting in syngeneic (group I; C3H→C3H) and allogeneic (group II, C57Bl/10J→C3H) animals served as controls. No morphological changes were evidenced in the transplanted aortas in group I animals. Contrarily, aortic allografts in group H animals underwent a self-limiting acute cellular rejection, which resolved completely and was succeeded by day 30 after transplantation by histopathological changes pathognomonic of chronic rejection. There was evidence for diffuse myointimal thickening, progressive concentric luminal narrowing, and patchy destruction of internal elastic membranes resulting in massive vascular obliteration by day 120 after transplantation. It was of interest that no arteriosclerotic changes were observed for the duration of follow-up (up to 120 days after transplantation) in transplanted aortas (liver donor-type) harvested from animals in group III. However, vasculopathy was prominent in third-party aortic grafts transplanted into tolerant recipients. Taken together, these data suggest that prior induction of tolerance abrogates the development of chronic rejection; this protection seems to be donor specific.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Subbotin, V Sun, H Aitouche, A Valdivia, LA Fung, JJ Starzl, TE tes11@pitt.edu TES11 Rao, AS
Centers:	Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute
Date:	15 September 1997
Date Type:	Publication
Journal or Publication Title:	Transplantation
Volume:	64
Number:	5
Page Range:	690 - 695
DOI or Unique Handle:	10.1097/00007890-199709150-00005
Institution:	University of Pittsburgh
Refereed:	Yes
ISSN:	0041-1337
Other ID:	uls-drl:31735062127091, Starzl CV No. 1987
Date Deposited:	08 Apr 2010 17:33
Last Modified:	22 Jun 2021 10:55
URI:	http://d-scholarship.pitt.edu/id/eprint/5373

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