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Allograft tolerance induced by donor apoptotic lymphocytes requires phagocytosis in the recipientCell death through apoptosis plays a critical role in regulating cellular homeostasis. Whether the disposal of apoptotic cells through phagocytosis can actively induce immune tolerance in vivo, however, remains controversial. Here, we report in a rat model that without using immunosuppressants, transfusion of apoptotic splenocytes from the donor strain prior to transplant dramatically prolonged survival of heart allografts. Histological analysis verified that rejection signs were significantly ameliorated. Splenocytes from rats transfused with donor apoptotic cells showed a dramatically decreased response to donor lymphocyte stimulation. Most importantly, blockade of phagocytosis in vivo, either with gadolinium chloride to disrupt phagocyte function or with annexin V to block binding of exposed phosphotidylserine to its receptor on phagocytes, abolished the beneficial effect of transfused apoptotic cells on heart allograft survival. Our results demonstrate that donor apoptotic cells promote specific allograft acceptance and that phagocytosis of apoptotic cells in vivo plays a crucial role in maintaining immune tolerance.
Document ID
20050185019
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
External Source(s)
Authors
Sun, E.
(Zhujiang Hospital Guangzhou 510282, China)
Gao, Y.
Chen, J.
Roberts, A. I.
Wang, X.
Chen, Z.
Shi, Y.
Date Acquired
August 23, 2013
Publication Date
December 1, 2004
Publication Information
Publication: Cell death and differentiation
Volume: 11
Issue: 12
ISSN: 1350-9047
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: AI43384
CONTRACT_GRANT: AI50222
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Regulatory Physiology
Non-NASA Center

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