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Costimulatory molecule-deficient dendritic cell progenitors (MHC class II<sup>+</sup>, CD80(dim), CD86<sup>-</sup>) prolong cardiac allograft survival in nonimmunosuppressed recipients

Fu, F and Li, Y and Qian, S and Lu, L and Chambers, F and Starzl, TE and Fung, JJ and Thomson, AW (1996) Costimulatory molecule-deficient dendritic cell progenitors (MHC class II<sup>+</sup>, CD80(dim), CD86<sup>-</sup>) prolong cardiac allograft survival in nonimmunosuppressed recipients. Transplantation, 62 (5). 659 - 665. ISSN 0041-1337

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Abstract

We have shown previously that granulocyte-macrophage colony-stimulating factor-stimulated mouse bone marrow-derived MHC class II + dendritic cell (DC) progenitors that are deficient in cell surface expression of the costimulatory molecules B7-1 (CD8O) and B7-2 (CD86) can induce alloantigen- specific T-cell anergy in vitro. To test the in vivo relevance of these findings, 2 x 10 6 B10 (H2(b)) mouse bone marrow-derived DC progenitors (NLDC 145 + , MHC class II + , B7-1(dim), B7-2(-/dim)) that induced T-cell hyporesponsiveness in vitro were injected systemically into normal C3H (H2(k)) recipients. Seven days later, the mice received heterotopic heart transplants from B10 donors. No immunosuppressive treatment was given. Median graft survival time was prolonged significantly from 9.5 to 22 days. Median graft survival time was also increased, although to a lesser extent (16.5 days), in mice that received third-party (BALB/c; H2(d)) DC progenitors. Ex vivo analysis of host T-cell responses to donor and third-party alloantigens 7 days after the injection of DC progenitors (the time of heart transplant) revealed minimal anti-donor mixed leukocyte reaction and cytotoxic T lymphocyte reactivity. These responses were reduced substantially compared with those of spleen cells from animals pretreated with 'mature' granulocyte- macrophage colony-stimulating factor + interleukin-4-stimulated DC (MHC class II(bright), B7-1 + , B7-2(bright)), many of which rejected their heart grafts in an accelerated fashion. Among the injected donor MHC class II + DC progenitors that migrated to recipient secondary lymphoid tissue were cells that appeared to have up-regulated cell surface B7-1 and B7-2 molecule expression. This observation may explain, at least in part, the temporary or unstable nature of the hyporesponsiveness induced by the DC progenitors in nonimmunosuppressed recipients.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Fu, F
Li, Y
Qian, S
Lu, L
Chambers, F
Starzl, TEtes11@pitt.eduTES11
Fung, JJ
Thomson, AW
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 15 September 1996
Date Type: Publication
Journal or Publication Title: Transplantation
Volume: 62
Number: 5
Page Range: 659 - 665
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0041-1337
Other ID: uls-drl:31735062133511, Starzl CV No. 1887
Date Deposited: 08 Apr 2010 17:32
Last Modified: 13 Oct 2017 22:56
URI: http://d-scholarship.pitt.edu/id/eprint/5273

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