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Prevention of chronic rejection in mouse aortic allografts by combined treatment with CTLA4-Ig and anti-CD40 ligand monoclonal antibody

Sun, H and Subbotin, V and Chen, C and Aitouche, A and Valdivia, LA and Sayegh, MH and Linsley, PS and Fung, JJ and Starzl, TE and Rao, AS (1997) Prevention of chronic rejection in mouse aortic allografts by combined treatment with CTLA4-Ig and anti-CD40 ligand monoclonal antibody. Transplantation, 64 (12). 1838 - 1843. ISSN 0041-1337

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Abstract

Background. In this study, using a murine model of aortic allotransplantation, the role of blockade of signaling through CD28/B7 and CD40/CD40 ligand costimulatory pathways in the evolvement of posttransplant vasculopathy was examined. Methods. Aortic allografts were transplanted across C57BL/10J (H2b)→C3H (H2(k)) strain combinations. Transient or more stable blockade of second signaling was achieved by either a single injection or multiple injections of CTLA4-Ig fusion protein (200 μg/dose i.p.) and/or anti-CD40 ligand (CD40L) monoclonal antibody (250 μg i.m.). At day 30 after transplantation, the grafts were harvested for histopathological and immunohistochemical examination. Results. Similar to allografts of untreated animals, aortic allografts obtained from recipients treated with either CTLA4-Ig or anti-CD40L monoclonal antibody alone exhibited marked narrowing of the lumen primarily due to concentric intimal thickening caused by proliferation of α-smooth muscle actin-positive cells. Contemporaneous treatment, however, with either a single injection or multiple injections of CTLA4-Ig and anti-CD40L monoclonal antibody resulted in marked diminution of intimal thickening. Interestingly, concurrent prolonged inhibition of CD28/B7 and CD40/ CD40L pathways resulted in complete abrogation of the development of posttransplant arteriopathy. Conclusion. These data suggest that a more stable disruption of signaling through costimulatory pathways may be required to obviate the development of posttransplant vasculopathy.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Sun, H
Subbotin, V
Chen, C
Aitouche, A
Valdivia, LA
Sayegh, MH
Linsley, PS
Fung, JJ
Starzl, TEtes11@pitt.eduTES11
Rao, AS
Centers: Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute
Date: 27 December 1997
Date Type: Publication
Journal or Publication Title: Transplantation
Volume: 64
Number: 12
Page Range: 1838 - 1843
DOI or Unique Handle: 10.1097/00007890-199712270-00035
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0041-1337
Other ID: uls-drl:31735062127802, Starzl CV No. 2059
Date Deposited: 08 Apr 2010 17:35
Last Modified: 22 Jun 2021 10:55
URI: http://d-scholarship.pitt.edu/id/eprint/5445

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