Document Detail


Blockade of the B7-CD28 pathway by CTLA4-Ig counteracts rejection and prolongs survival in small bowel transplantation.
MedLine Citation:
PMID:  10736090     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Allograft rejection involves T-cell activation, requiring T-cell receptor interactions with major histocompatibility complex (MHC) molecules and costimulatory signals delivered through the B7-CD28 pathway. We evaluated the effect of blocking this pathway on graft rejection and survival, in a rat experimental model of small bowel transplantation. Heterotopic small bowel transplantation was performed between PVG donor rats and DA recipient rats. The recipient animals were treated with CTLA4-Ig or irrelevant immunoglobulin (Ig)G as control and followed for 18, 30 or 90 days. The survival rate and degree of inflammation and accumulation of CD4+ T cells and macrophages were determined in the transplanted bowels. We found that administration of CTLA4-Ig significantly improved the survival rate compared to control rats: after 30 days 73% of the treated rats had survived and at 90 days 5/8 rats were still living, whereas in the control group only 2/8 rats had survived. The grafts showed preserved mucosal structure with only a mild degree of subacute inflammation and the accumulation of CD4+ T cells and macrophages was noticeably reduced in treated animals as compared to control rats. Necrosis was extensive in control rats, whereas CTLA4-Ig treated animals had grafts with at least some preserved villus morphology and no necrotic tissue. Although small bowel transplantation has proven exceptionally difficult, in this study we have shown that CTLA4-Ig treatment may provide a promising strategy to prevent rejection and induce long term tolerance and graft survival.
Authors:
G Kurlberg; E Haglind; K Schön; H Törnqvist; N Lycke
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Scandinavian journal of immunology     Volume:  51     ISSN:  0300-9475     ISO Abbreviation:  Scand. J. Immunol.     Publication Date:  2000 Mar 
Date Detail:
Created Date:  2000-04-04     Completed Date:  2000-04-04     Revised Date:  2013-05-24    
Medline Journal Info:
Nlm Unique ID:  0323767     Medline TA:  Scand J Immunol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  224-30     Citation Subset:  IM    
Affiliation:
Departments of Surgery and Medical Microbiology and Immunology, University of Göteborg, S-413 45 Göteborg, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD
Antigens, CD28 / immunology*
Antigens, CD80 / immunology*
Antigens, Differentiation / therapeutic use*
CTLA-4 Antigen
Cell Movement / immunology
Enteritis / immunology,  pathology,  prevention & control
Graft Rejection / immunology,  mortality,  pathology,  prevention & control*
Graft Survival / immunology*
Immunoconjugates*
Immunosuppressive Agents / therapeutic use*
Intestinal Mucosa / immunology,  pathology,  transplantation
Intestine, Small / immunology,  pathology,  transplantation*
Macrophages / immunology,  pathology
Necrosis
Rats
Rats, Inbred Strains
Signal Transduction / immunology
Survival Rate
T-Lymphocytes / immunology,  pathology
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, CD28; 0/Antigens, CD80; 0/Antigens, Differentiation; 0/CTLA-4 Antigen; 0/Ctla4 protein, rat; 0/Immunoconjugates; 0/Immunosuppressive Agents; 7D0YB67S97/abatacept

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