Document Detail

Feasibility of immunosuppression in composite tissue allografts by systemic administration of CTLA4Ig.
MedLine Citation:
PMID:  11884927     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Although recent experimental studies have demonstrated CTLA4Ig to be a potent immunosuppressant in vascularized solid organ allografts, little attention has been given to the effect of this soluble recombinant fusion protein on immunosuppression in composite tissue allografts (CTAs). Using a rat hind limb allograft model, we examined the efficacy of CTLA4Ig against the allograft rejection of composite tissue.
METHODS: The hind limbs of ACI rats (RT1a) were heterotopically transplanted to Lewis rats (RT11). Controls received no immunotherapy. Experimental recipients were treated with a single i.p. injection of either human immunoglobulin (Ig)G (0.5 mg/body) or CTLA4Ig (0.5 mg/body) according to different time schedules. Graft survival time and histopathological changes for each experimental group were evaluated and statistically compared.
RESULTS: Graft survival times were prolonged significantly in rats treated with CTLA4Ig on day 1 and day 2 after transplantation, compared with survival times of controls. In particular, the most significant prolongation was found in rats treated on day 2. At 7 days after transplantation, moderate-to-severe histological rejection occurred in all tissues in control rats. On the other hand, in rats treated with CTLA4Ig, all tissues showed significantly better preservation. Among these treated rats, the rats treated on day 2 showed excellent histopathological conditions in each tissue.
CONCLUSIONS: This study supports the feasibility of using CTLA4Ig for preventing acute rejection in CTA. On the basis of the current results, the administration of CTLA4Ig for CTA is more effective at 24-48 hr after transplantation, after the initial immune response has been allowed to begin.
Norimasa Iwasaki; Taketoshi Gohda; Chika Yoshioka; Masaaki Murakami; Manabu Inobe; Akio Minami; Toshimitsu Uede
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Transplantation     Volume:  73     ISSN:  0041-1337     ISO Abbreviation:  Transplantation     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-03-08     Completed Date:  2002-03-21     Revised Date:  2013-05-24    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  334-40     Citation Subset:  IM    
Department of Orthopaedic Surgery, Hokkaido University School of Medicine, Hokkaido University, Sapporo 060-8638, Japan.
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MeSH Terms
Antigens, CD
Antigens, Differentiation / therapeutic use*
CTLA-4 Antigen
Graft Rejection / prevention & control
Graft Survival
Graft vs Host Disease / etiology
Hindlimb / transplantation
Immune Tolerance
Immunosuppressive Agents / therapeutic use*
Rats, Inbred ACI
Rats, Inbred Lew
T-Lymphocytes / immunology
Transplantation, Homologous / immunology*
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, Differentiation; 0/CTLA-4 Antigen; 0/CTLA4 protein, human; 0/Ctla4 protein, rat; 0/Immunoconjugates; 0/Immunosuppressive Agents; 7D0YB67S97/abatacept
Comment In:
Transplantation. 2003 Jul 27;76(2):438; author reply 438-9   [PMID:  12883212 ]

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

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