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Split tolerance induced by orthotopic liver transplantation in MICE

Dahmen, U and Qian, S and Rao, AS and Demetris, AJ and Fu, F and Sun, H and Gao, L and Fung, JJ and Starzl, TE (1994) Split tolerance induced by orthotopic liver transplantation in MICE. Transplantation, 58 (1). 1 - 8. ISSN 0041-1337

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Spontaneous orthotopic liver allograft acceptance associated with microchimerism in mice induces tolerance to subsequent skin or heart transplants from the donor but not third-party animals. Despite in vivo hyporesponsiveness, in vitro MLC and CTL assays showed continuing antidonor reactivity. Cells isolated from recipients’ spleens and grafted livers, when tested in MLC and CTL assays, were antidonor reactive out to 3 months to the same degree as splenocytes obtained from either naive or presensitized (with skin or heart) mice. Nevertheless, passive transfer of splenocytes or liver lymphocytes from liver tolerant mice, but not naive or sensitized donor strain mice, were able to prolong skin graft survival significantly in naive irradiated recipients. By using a strain combination in which the donor but not the recipient expressed the stimulatory endogenous super-Ag (Mlsf), it was possible to determine whether super-Ag-reactive T cells bearing Vß5 and Vβll were deleted or anergic. Phenotypic analysis of cells isolated from recipients’ spleens and grafted livers (up to 90 days after transplant), when compared with naive animals, showed no significant difference in Vß5 and Vβll TCR expression. Additionally, when these isolated spleen cells were tested for antibody-mediated stimulation, both anti-Vß5 and Vβll TCR mAb led to marked proliferation of cells obtained from naive and liver-trans-planted recipients, but as expected, proliferation was very low in cells from naive donors. These results suggest that liver transplantation induces donor-specific tolerance in vivo, which may not be reflected in in vitro proliferative and cytotoxicity assays (split tolerance). Furthermore, this tolerance does not seem to be induced by clonal deletion or anergy of minor-lymphocyte-stimulating-antigen-reactive T cells in the recipients. © 1994 by Williams and Wilkins.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Dahmen, U
Qian, S
Rao, AS
Demetris, AJ
Fu, F
Sun, H
Gao, L
Fung, JJ
Starzl, TEtes11@pitt.eduTES11
Centers: Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 January 1994
Date Type: Publication
Journal or Publication Title: Transplantation
Volume: 58
Number: 1
Page Range: 1 - 8
DOI or Unique Handle: 10.1097/00007890-199407150-00001
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0041-1337
Other ID: uls-drl:31735062118827, Starzl CV No. 1329
PubMed ID: 8036695
Date Deposited: 08 Apr 2010 17:22
Last Modified: 16 Aug 2020 09:55


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