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Marked mitigation of transplant vascular sclerosis in FasL(gld) (CD95L) mutant recipients. I. The role of alloantibodies in the development of chronic rejection

Subbotin, V and Sun, H and Aitouche, A and Salam, A and Valdivia, LA and Fung, JJ and Starzl, TE and Rao, AS (1999) Marked mitigation of transplant vascular sclerosis in FasL(gld) (CD95L) mutant recipients. I. The role of alloantibodies in the development of chronic rejection. Transplantation, 67 (10). 1295 - 1300. ISSN 0041-1337

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Abstract

Background. In the acute rejection of allografts, the interaction between Fas (CD95) and its ligand (FasL; CD95L) has been shown to be involved in mediating apoptotic cell death. The role, however, of these molecules in the pathogenesis of transplant vascular sclerosis is as yet undetermined. The present study was therefore designed to address this issue. Material. C3H/HEJ FasL(gld) (FasL - ; H2(k)) spontaneously mutant mice were used either as donors or recipients of aortic allografts; wild-type C57BI/6 (B6; H2 b ) were used as corresponding recipients or donors (n=6/group), respectively. Controls included aortas transplanted across appropriate allogeneic and syngeneic strain combinations. For histopathological evaluations, the grafts were harvested at day 40 after transplantation, at which time, splenocytes and sera were also obtained for mixed leukocyte reaction and complement- mediated microcytotoxicity assays, respectively. Results. Similar to aortas obtained from allogeneic controls, allografts harvested from FasL - →B6 recipients had morphological evidence of chronic rejection characterized by circumferential intimal thickening with partial disruption of the elastic membranes. Correspondingly, heightened antidonor cellular reactivity was also witnessed in these recipients. On the contrary, B6 allografts harvested from the majority of C3H→FasL - recipients exhibited marked preservation of aortic morphology. Although these recipients had diminished antidonor cellular proliferation, the titers of alloantibodies were markedly elevated. Conclusion. The presence of FasL-expressing functional cytotoxic T cells is required for the pathogenesis of transplant vascular sclerosis. The significant reduction and/or absence of chronic rejection with the concomitant retention of antidonor humoral response in C3H FasL - recipients of B6 aortas prompt us to suggest that perhaps posttransplantation vasculopathy is initiated by cell-mediated cytotoxicity with its perpetuation facilitated by alloantibodies.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Subbotin, V
Sun, H
Aitouche, A
Salam, A
Valdivia, LA
Fung, JJ
Starzl, TEtes11@pitt.eduTES11
Rao, AS
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 27 May 1999
Date Type: Publication
Journal or Publication Title: Transplantation
Volume: 67
Number: 10
Page Range: 1295 - 1300
DOI or Unique Handle: 10.1097/00007890-199905270-00001
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0041-1337
Other ID: uls-drl:31735062120047, Starzl CV No. 2095
Date Deposited: 08 Apr 2010 17:35
Last Modified: 13 Oct 2017 21:58
URI: http://d-scholarship.pitt.edu/id/eprint/5481

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