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Lymphoid/nonlymphoid compartmentalization of donor leukocyte chimerism in rat recipients of heart allografts, with or without adjunct bone marrow

Terakura, M and Murase, N and Demetris, AJ and Ye, Q and Thomson, AW and Starzl, TE (1998) Lymphoid/nonlymphoid compartmentalization of donor leukocyte chimerism in rat recipients of heart allografts, with or without adjunct bone marrow. Transplantation, 66 (3). 350 - 357. ISSN 0041-1337

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Abstract

Background. The role of leukocyte migration and chimerism in organ allograft acceptance has been obscured by the lack of information about the late localization of the donor cells. Methods. Male Lewis rat→female Brown Norway abdominal heart transplantation was performed under tacrolimus immunosuppression (days 0-13, 20, and 27) with or without donor bone marrow and (in bone marrow subgroups) a 1-week postoperative course of a possibly chimerism-enhancing drug. Using rat sex-determining region-Y-specific oligonucleotide primers, we determined the donor DNA concentration by polymerase chain reaction in serial venous blood sampies for 100 days and in tissue specimens when animals were killed. Results. Chimerism was detected out to 56 days in 89% of the blood samples but in none of the samples at 100 days. However, donor DNA was detected when animals were killed in 95% of the native hearts, 80% of the skin biopsy specimens, and 23% of the spleens. The presence and quantity of early and late chimerism were strongly correlated the administration of adjunct bone marrow and with a reduction in the vasculopathy and inflammation index in the cardiac allografts. Marginally significant further increases in chimerism and/or reductions in chronic heart rejection beyond those achieved with adjunct bone marrow alone were associated with additional treatment with the growth factors Flt-3 ligand, granulocyte colonystimulating factor, and a recombinant molecular variant of interleukin-6 (interleukin-6 mutein) but not with hepatocyte growth factor or lisofylline. Conclusions. The previously suspected shift of early chimerism in the blood and lymphoid organs to dominance in host nonlymphoid tissues is consistent with the dual mechanisms of clonal exhaustion and immune indifference, governed by antigen migration and localization, that have been postulated elsewhere to account for organ allograft acceptance.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Terakura, M
Murase, N
Demetris, AJ
Ye, Q
Thomson, AW
Starzl, TEtes11@pitt.eduTES11
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 15 August 1998
Date Type: Publication
Journal or Publication Title: Transplantation
Volume: 66
Number: 3
Page Range: 350 - 357
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0041-1337
Other ID: uls-drl:31735062127406, Starzl CV No. 2019
Date Deposited: 08 Apr 2010 17:34
Last Modified: 13 Oct 2017 22:58
URI: http://d-scholarship.pitt.edu/id/eprint/5405

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