Document Detail

Suppression of T cells results in long-term survival of mouse heart xenografts in C6-deficient rats.
MedLine Citation:
PMID:  11737856     Owner:  NLM     Status:  MEDLINE    
The present study aimed to investigate the role of cellular immune response in the absence of membrane attack complex (MAC) formation in the concordant mouse-to-rat heart xenografting. Hearts from BALB/c mice were transplanted into the neck vessels of C6-competent (C6(+)) and C6-deficient (C6(-)) PVG rats. Liposome-encapsulated dichloro-methylene diphosphonate (Lip-Cl2MDP) was administered at a dose of 10 ml/kg 2 days before transplantation and every 5 days thereafter. Cyclosporine (CsA) was administered intramuscularly (i.m.) at a dose of 15 mg/kg per day. The heart xenografts were harvested for immuno-histological analysis at the time of rejection and the functioning grafts were removed at 70 days after transplantation. In untreated C6(+) rats, xeno-grafts survived for 2.3 +/- 0.5 days. Treatment with CsA or Lip-Cl(2)MDP in C6(+) rats did not significantly affect graft survival (2.5 +/- 0.6 and 2.3 +/- 0.4 days, respectively). In untreated C6(-) rats, xenografts survived for 5.0 +/- 0.6 days. However, Lip-Cl(2)MDP in C6(-) rats resulted in a prolongation of graft survival to 11 +/- 2.3 days (P < 0.05 vs. untreated C6(-) rats), while treatment with CsA alone in these rats led to more than 70 days' survival in four out of six grafts (61 +/- 16 days). In untreated C6(+) rats, immunohistology showed a severe myocardial necrosis and thrombosis with a scarce cellular infiltrate in the rejected xenografts. By contrast, in untreated C6(-) rats, xenografts were heavily infiltrated by macrophages and T cells. The number of macrophages, but not T cells, was markedly reduced in Lip-Cl(2)MDP-treated rats. In CsA-treated C6(-) rats, the grafts harvested at 70 days after transplantation had a normal morphology, with a minimal cellular infiltrate. Our data indicate that MAC-mediated injury plays an essential role in concordant xenograft rejection. Once this mechanism has been prevented, suppression of T cells allows for long-term xenograft survival.
G Wu; O Korsgren; N van Rooijen; A Tibell
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Xenotransplantation     Volume:  8     ISSN:  0908-665X     ISO Abbreviation:  Xenotransplantation     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-12-13     Completed Date:  2002-04-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9438793     Medline TA:  Xenotransplantation     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  303-9     Citation Subset:  IM    
Department of Transplantation Surgery, Huddinge Hospital, Karolinska Institute, Stockholm, Sweden.
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MeSH Terms
Animals, Genetically Modified
Clodronic Acid / pharmacology
Complement C3 / analysis
Complement C6 / deficiency*,  physiology
Cyclosporine / pharmacology
Graft Rejection / immunology,  pathology,  prevention & control*
Graft Survival / immunology*
Heart Transplantation / immunology*
Immunity, Cellular
Immunoglobulin G / analysis
Immunoglobulin M / analysis
Immunosuppressive Agents / pharmacology
Killer Cells, Natural / immunology
Macrophages / immunology
Mice, Inbred BALB C
Myocardial Contraction
Myocardium / immunology,  pathology
T-Lymphocyte Subsets / immunology*
Transplantation, Heterologous / immunology*
Transplantation, Heterotopic
Reg. No./Substance:
0/Complement C3; 0/Complement C6; 0/Immunoglobulin G; 0/Immunoglobulin M; 0/Immunosuppressive Agents; 0/Liposomes; 10596-23-3/Clodronic Acid; 59865-13-3/Cyclosporine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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