Document Detail

CTLA4-Ig abrogates the anti-globulin response and prolongs cardiac allograft survival after anti-CD2 treatment.
MedLine Citation:
PMID:  14551027     Owner:  NLM     Status:  MEDLINE    
CD2 is expressed on T cells and NK cells and is important in T cell activation, making it a potential target for immune intervention. Here, we report a series of experiments aimed at defining the ability of mAbs directed against the CD2 molecule to prevent cardiac allograft rejection in low and high responder rat strain combinations. Administration of the mouse anti-rat CD2 mAbs OX34 or OX55 around the time of transplantation prolonged survival of fully allogeneic Lewis (RT1l) cardiac allografts in low responder DA (RT1a) recipients (MST 14 days for OX55 and >100 days for OX34). Treatment with OX34 prolonged graft survival in the reciprocal high responder DA to Lewis rat strain combination (MST 19 days) and when combined with CTLA4-Ig resulted in long-term graft survival (MST>100 days). Despite these in vivo effects, OX34 had little effect on in vitro assays of lymphocyte activation. Instead, the ability of OX34 to extend allograft survival correlated with T cell depletion. Administration of OX34 induced a similar degree of CD4 T cell depletion in DA and Lewis recipients, but the CD4 depletion observed was more transient in Lewis recipients. Lewis, but not DA strain rats, developed an anti-murine Ig response. Combined treatment with CTLA4-Ig abolished the anti-globulin response to OX34 in Lewis recipients, prolonged circulation of OX34 and increased the extent and duration of CD4 depletion. We conclude that anti-CD2 treatment effectively prolongs cardiac allograft survival and addition of CTLA4-Ig increases its efficacy by abrogating the production of neutralising antibodies.
David Stell; Hilary Marshall; J Andrew Bradley; Eleanor M Bolton
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Transplant immunology     Volume:  12     ISSN:  0966-3274     ISO Abbreviation:  Transpl. Immunol.     Publication Date:    2003 Oct-Nov
Date Detail:
Created Date:  2003-10-10     Completed Date:  2004-06-14     Revised Date:  2013-05-24    
Medline Journal Info:
Nlm Unique ID:  9309923     Medline TA:  Transpl Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1-7     Citation Subset:  IM    
University Department of Surgery, Western Infirmary, Glasgow G11 6NT, UK.
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MeSH Terms
Antibodies, Monoclonal / pharmacology,  therapeutic use*
Antibody Formation / drug effects*
Antigens, CD2 / immunology*
CD4-CD8 Ratio
CD4-Positive T-Lymphocytes / drug effects
CD8-Positive T-Lymphocytes / drug effects
Graft Survival / drug effects,  immunology*
Heart Transplantation / immunology*
Immunoconjugates / pharmacology*
Interferon-gamma / analysis
Interleukin-2 / analysis
Lymphocyte Culture Test, Mixed
Rats, Inbred Lew
Receptors, Antigen, T-Cell, alpha-beta / immunology
T-Lymphocytes, Cytotoxic / drug effects
Transplantation, Homologous / immunology
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD2; 0/Immunoconjugates; 0/Interleukin-2; 0/Receptors, Antigen, T-Cell, alpha-beta; 7D0YB67S97/abatacept; 82115-62-6/Interferon-gamma

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

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