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Apoptosis Within Spontaneously Accepted Mouse Liver Allografts: Evidence for Deletion of Cytotoxic T Cells and Implications for Tolerance Induction

Qian, S and Lu, L and Fu, F and Li, Y and Li, W and Starzl, TE and Fung, JJ and Thomson, AW (1997) Apoptosis Within Spontaneously Accepted Mouse Liver Allografts: Evidence for Deletion of Cytotoxic T Cells and Implications for Tolerance Induction. Journal of Immunology, 158 (10). 4654 - 4661. ISSN 0022-1767

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Abstract

MHC-mismatched liver grafts are accepted spontaneously between many mouse strains. The underlying mechanism(s) is unclear. In the B10 (H2b) to C3H (H2k) strain combination used in this study, donor T cells within the liver were rapidly replaced within 2 to 4 days of transplantation with those of the recipient. Freshly isolated liver graft-infiltrating cells harvested on days 4 and 7 exhibited strong CTL responses against donor alloantigens. CTL activity was reduced substantially, however, by day 14, although levels of CTL precursors in the spleen and liver remained high. Examination of the liver allografts by in situ terminal deoxynucleotidyltransferase-catalyzed dUTP-digoxigenin nick end labeling on days 4, 7, and 14 after transplantation revealed prominent apoptotic cells dispersed throughout the nonparenchymal cell population. When acute liver allograft rejection was induced by administration of IL-2 from days 0 to 4 post-transplant (median survival time, 5 days), apoptotic activity (day 4) was reduced substantially, whereas CTL activity was enhanced. Nonparenchymal cells isolated from allografts of unmodified recipients 4, 7, and 14 days after transplantation exhibited significantly higher DNA fragmentation after 18-h culture than cells from liver isografts. Moreover, the level was 4 to 5 times higher than that of cells from IL-2-treated mice (on day 4). These observations suggest that T cell deletion, not regulation, may be responsible for spontaneous liver allograft acceptance. The molecular recognition events that cause apoptosis of infiltrating T cells and why this occurs within liver grafts, but not heart or skin grafts, remain to be elucidated.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Qian, S
Lu, L
Fu, F
Li, Y
Li, W
Starzl, TEtes11@pitt.eduTES11
Fung, JJ
Thomson, AW
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 15 May 1997
Date Type: Publication
Journal or Publication Title: Journal of Immunology
Volume: 158
Number: 10
Page Range: 4654 - 4661
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0022-1767
Other ID: uls-drl:31735062134188, Starzl CV No. 1961
Date Deposited: 08 Apr 2010 17:33
Last Modified: 25 Jan 2019 23:55
URI: http://d-scholarship.pitt.edu/id/eprint/5347

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