Document Detail

Permanent acceptance of liver allografts by intraportal injection of donor spleen cells in rats.
MedLine Citation:
PMID:  1595063     Owner:  NLM     Status:  MEDLINE    
Antigen pretreatment through the oral or intraportal route has been reported to suppress antibody formation or delayed-type hypersensitivity (DTH) response to the same antigens. However, this effect on allografted organs has not been well studied. In this study we evaluated the efficacy for suppression of antibody formation and DTH response to the allogeneic antigens and tried to prolong liver allograft survival in rats. Male ACI (RT1a) rats were used as donors and male BUF (RT1b) rats as recipients. Intraportal or intravenous injection of spleen cells (SPCs) (5 x 10(7)) was performed through the mesenteric vein or the tail vein, respectively. The anti-ACI DTH response was tested by ear challenge of ACI SPCs. Cytotoxic antibody was assessed by complement-dependent cytotoxicity assay. ACI rat liver was transplanted orthotopically to BUF rat by the cuff technique 10 days after SPC injection. Cytotoxic antibody titer rose to X2(6) to X2(8) at 7 to 10 days after intravenous injection of SPCs. However, intraportal injection of the cells rarely caused a rise in antibody titer and even strongly suppressed subsequent antibody formation induced by intravenous injection when given 10 days before. The DTH response was also suppressed by intraportal injection of SPCs, with a mean value of 0.18 +/- 0.13 mm versus 0.67 +/- 0.19 mm for controls or 0.46 +/- 0.04 mm with intravenous injection. Liver-allografted rats died between 9 and 11 days, averaging 10.1 +/- 0.7 days in the control group. All seven transplants injected intraportally with donor SPCs survived more than 100 days, whereas six of eight rats injected intravenously with donor SPCs died of bleeding from the surface of the liver grafts within 12 hours after grafting, with signs similar to those of hyperacute rejection. Four of five rats injected intraportally with F344 (third-party) SPCs died of acute rejection in the same way the control rats died. The liver allograft-bearing rats had permanently accepted ACI skin grafts when tested 60 days after liver transplantation but rejected F344 skin grafts in the normal fashion. Intraportal injection of donor SPCs markedly suppressed the antibody formation, as well as the DTH response, and completely blocked liver allograft rejection. Moreover, the liver allograft-bearing rats proved to be fully tolerant of the donor antigen. This method might be a promising modality for inducing donor-specific tolerance in liver transplantation.
Y Nakano; M Monden; L A Valdivia; M Gotoh; T Tono; T Mori
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Surgery     Volume:  111     ISSN:  0039-6060     ISO Abbreviation:  Surgery     Publication Date:  1992 Jun 
Date Detail:
Created Date:  1992-07-02     Completed Date:  1992-07-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0417347     Medline TA:  Surgery     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  668-76     Citation Subset:  AIM; IM    
Department of Surgery II, Osaka University Medical School, Japan.
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MeSH Terms
Antibody Formation
Antigens / physiology
Graft Survival*
Hypersensitivity, Delayed / immunology
Immunosuppression / methods*
Injections, Intravenous
Liver / cytology
Liver Transplantation*
Lymphoid Tissue / transplantation
Portal Vein
Rats, Inbred BUF
Rats, Inbred F344
Rats, Inbred Strains
Spleen / cytology*,  immunology
Transplantation, Homologous
Reg. No./Substance:

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