Document Detail


Rapamycin-induced long-term allograft survival depends on persistence of alloantigen.
MedLine Citation:
PMID:  8144906     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In this study the mechanism of rapamycin-induced long-term allograft tolerance was investigated in a rat model. We have demonstrated that the tolerance is strain specific, but is not organ specific. The tolerized rats failed to generate high levels of donor-specific cytotoxic Ab and cytotoxic cells in vivo. Removal of the alloantigen from the tolerized rats with or without concomitant thymectomy could break down the status of tolerance, and the rats regained the capability to reject the grafts and to develop specific cytotoxic Ab and cytotoxic cells. These results clearly indicate that the maintenance of the rapamycin-induced long-term tolerance to allografts depends on the persistence of alloantigens. Mechanistically, we have shown that the reduced IL-2 production and the reduced antigenicity of the graft in the tolerized rat contribute to, but are not solely responsile for, the tolerance. The results of adoptive transfer experiments suggest that regulatory cells or suppressive serum factors are not involved in the tolerance. The fact that the removal of the alloantigen in the thymectomized rat could reverse the tolerance, indicates that there is no clonal deletion. We propose that chronic desensitization due to prolonged engagement of TCR by persistent alloantigens is the major mechanism at the late stage of the rapamycin-induced allograft tolerance.
Authors:
H Chen; H Luo; P Daloze; D Xu; J Wu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  152     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  1994 Mar 
Date Detail:
Created Date:  1994-05-04     Completed Date:  1994-05-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3107-18     Citation Subset:  AIM; IM    
Affiliation:
Laboratory of Experimental Surgery, Notre-Dame Hospital Research Center, Montreal, Quebec, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibody Formation
Graft Survival / drug effects*
Immune Tolerance
Immunosuppressive Agents / pharmacology*
Interleukin-2 / biosynthesis
Isoantigens / physiology*
Male
Organ Specificity
Polyenes / pharmacology*
Rats
Rats, Inbred BUF
Rats, Inbred Lew
Rats, Inbred WF
Sirolimus
T-Lymphocytes, Regulatory / physiology
Transplantation, Homologous
Chemical
Reg. No./Substance:
0/Immunosuppressive Agents; 0/Interleukin-2; 0/Isoantigens; 0/Polyenes; 53123-88-9/Sirolimus

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