Document Detail

Combination of donor-specific blood transfusion with anti-CD28 antibody synergizes to prolong graft survival in rat liver transplantation.
MedLine Citation:
PMID:  17175236     Owner:  NLM     Status:  MEDLINE    
Donor-specific blood transfusion (DST) has been shown to effectively induce tolerance to certain allografts. In addition, it is well known that blockade of costimulatory signals reduces the ability of T cells to respond to alloantigens, prolonging allograft survival in some transplant models. We assessed the effects of single or multiple DSTs in the absence or presence of anti-CD28 monoclonal antibodies (mAbs) on graft function and host survival in rat liver transplantation (LTx). Fully MHC-mismatched adult male Dark Agouti (DA) and Lewis (LEW) rats were used as donors and recipients, respectively. Heparinized DA blood was administered to naïve LEW rats 7 days before LTx [DST(-7d)], 14 and 7 days before LTx [DST(1 x 2)], twice a week for 2 weeks prior to LTx [DST(2 x 2)] and once a week for 4 weeks prior to LTx [DST(1 x 4)]. For some experiments, two different monoclonal antibodies (mAb) to rat CD28 (JJ316 and JJ319) were administered in combination with some DST treatments. We found that DST administration induced a time- and dose-dependent increase in host survival. Treatment of LEW rats with JJ316 or JJ319 mAb alone failed to prolong graft survival over untreated rats; however, the combination of DST(1 x 2) with JJ316 or JJ319 mAb induced indefinite survival at 100 days following surgery. We found that this protective effect was associated with increased numbers of splenic CD4+ CD45RC- but not CD4+ CD25+ foxp3+ T-cells in long-term survivors. Our data suggest that the combination of suboptimal DST with CD28 mAb induces donor-specific tolerance that correlates with enhanced numbers of regulatory T-cells.
H Urakami; D V Ostanin; T Hünig; M B Grisham
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Transplantation proceedings     Volume:  38     ISSN:  0041-1345     ISO Abbreviation:  Transplant. Proc.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-12-18     Completed Date:  2007-04-30     Revised Date:  2012-10-09    
Medline Journal Info:
Nlm Unique ID:  0243532     Medline TA:  Transplant Proc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3244-6     Citation Subset:  IM    
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.
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MeSH Terms
Antibodies, Monoclonal / therapeutic use*
Antigens, CD28 / immunology*
Blood Transfusion*
Graft Survival / immunology*
Liver Transplantation / immunology*
Rats, Inbred Lew
Rats, Inbred Strains
Tissue Donors
Grant Support
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD28

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