Document Detail

Allograft tolerance induced by donor apoptotic lymphocytes requires phagocytosis in the recipient.
MedLine Citation:
PMID:  15375386     Owner:  NLM     Status:  MEDLINE    
Cell 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.
E Sun; Y Gao; J Chen; A I Roberts; X Wang; Z Chen; Y Shi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cell death and differentiation     Volume:  11     ISSN:  1350-9047     ISO Abbreviation:  Cell Death Differ.     Publication Date:  2004 Dec 
Date Detail:
Created Date:  2004-11-15     Completed Date:  2005-06-17     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9437445     Medline TA:  Cell Death Differ     Country:  England    
Other Details:
Languages:  eng     Pagination:  1258-64     Citation Subset:  IM; S    
Transplantation Department, Zhujiang Hospital, Guangzhou 510282, China.
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MeSH Terms
Annexin A5 / pharmacology
Apoptosis / immunology*
Gadolinium / pharmacology
Graft Rejection / immunology,  prevention & control
Graft Survival / immunology*
Heart Transplantation / immunology
Lymphocyte Transfusion / methods*
Lymphocytes / immunology*
Models, Animal
Phagocytosis / immunology*
Rats, Sprague-Dawley
Rats, Wistar
Receptors, Cell Surface / antagonists & inhibitors,  metabolism
Transplantation Tolerance / immunology*
Grant Support
Reg. No./Substance:
0/Annexin A5; 0/Receptors, Cell Surface; 0/phosphatidylserine receptor; 10138-52-0/gadolinium chloride; 7440-54-2/Gadolinium
Y Shi / U Med Dentistry NY, Piscataway

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