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Allogeneic hematolymphoid microchimerism and prevention of autoimmune disease in the rat: A relationship between allo- and autoimmunity

Delaney, CP and Murase, N and Chen-Woan, M and Fung, JJ and Starzl, TE and Demetris, AJ (1996) Allogeneic hematolymphoid microchimerism and prevention of autoimmune disease in the rat: A relationship between allo- and autoimmunity. Journal of Clinical Investigation, 97 (1). 217 - 225. ISSN 0021-9738

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Abstract

Conventional allogeneic bone marrow transplantation after myeloablation can prevent experimental autoimmunity and has been proposed as treatment for humans. However, trace populations of donor hematolymphoid cells persisting in solid organ allograft recipients have been associated in some circumstances with therapeutic effects similar to replacement of the entire bone marrow. We therefore examined whether inducing hematolymphoid microchimerism without myeloablation could confer the ability to resist mercuric chloride (HgCl 2 )-induced autoimmunity. Brown-Norway (BN) rats were pretreated with a syngeneic or allogeneic bone marrow infusion under transient FK506 immunosuppression before receiving HgCl 2 . They were compared with BN rats receiving either no pretreatment (naive) or FK506 alone. Administration of HgCl 2 to naive BN rats induced marked autoantibody production, systemic vasculitis and lymphocytic infiltration of the kidneys, liver and skin in all of the animals and a 47% mortality. In contrast, BN rats pretreated with HgCl 2 -resistant allogeneic Lewis bone marrow and transient FK506 showed less clinical disease and were completely protected from mortality. More specifically, IgG anti-laminin autoantibody production was decreased by 40% (P < 0.05), and there was less histopathological tissue injury (P < 0.005), less in vitro autoreactivity (P < 0.05), less of an increase in class II MHC expression on B cells (P < 0.01), and 22% less weight loss (P < 0.01), compared with controls. Protection from the experimental autoimmunity was associated with signs of low grade activation of the BN immune system, which included: increased numbers of circulating B and activated T cells before administration of HgCl 2 , and less autoreactivity and spontaneous proliferation in vitro after HgCl 2 .


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Delaney, CP
Murase, N
Chen-Woan, M
Fung, JJ
Starzl, TEtes11@pitt.eduTES11
Demetris, AJ
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 January 1996
Date Type: Publication
Journal or Publication Title: Journal of Clinical Investigation
Volume: 97
Number: 1
Page Range: 217 - 225
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0021-9738
Other ID: uls-drl:31735062121656, Starzl CV No. 1817
Date Deposited: 08 Apr 2010 17:31
Last Modified: 13 Oct 2017 21:57
URI: http://d-scholarship.pitt.edu/id/eprint/5203

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