Document Detail

Modulation of the CD2 receptor and not disruption of the CD2/CD48 interaction is the principal action of CD2-mediated immunosuppression in the rat.
MedLine Citation:
PMID:  9427810     Owner:  NLM     Status:  MEDLINE    
CD48, the murine homolog of human CD58, binds to CD2 in rats and mice. Whereas inhibition of CD2 signaling leads to profound immunosuppression, no information is available on CD48-targeted therapy in the rat. We could show that anti-CD2 treatment (OX34) efficiently inhibited TCR-driven as well as CD2-mediated proliferation, whereas blocking of ligand binding (OX45) remained completely uneffective. Inhibition of allogeneic MLR by OX45 turned out to be due to induction of unspecific suppressive mechanisms. In vivo, OX45 failed to prolong rat heart allograft survival in contrast to that seen with OX34. Grafts were rejected despite persistent and complete downmodulation of CD48 on lymphocytes without any cell depleting effect, rendering receptor/ligand interactions physically impossible. Combined application of CD2 and CD48 mAb did not enhance immunosuppression induced by CD2 mAb alone. Provided that there is no alternative CD2 ligand in the rat, we conclude that CD2-directed immunotherapy is mediated by suppressive events induced by modulation of the CD2 receptor ("negative signaling") rather than by mere disruption of the CD2-CD48 interaction.
B Sido; G Otto; R Zimmermann; P Müller; S C Meuer; T J Dengler
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cellular immunology     Volume:  182     ISSN:  0008-8749     ISO Abbreviation:  Cell. Immunol.     Publication Date:  1997 Nov 
Date Detail:
Created Date:  1998-01-27     Completed Date:  1998-01-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1246405     Medline TA:  Cell Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  57-67     Citation Subset:  IM    
Department of Surgery, University of Heidelberg, Germany.
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MeSH Terms
Antibodies, Monoclonal / pharmacology
Antigens, CD / metabolism*
Antigens, CD2 / metabolism*
Graft Survival / immunology
Heart Transplantation / immunology
Immune Tolerance
Lymphocyte Activation
Lymphocyte Culture Test, Mixed
Rats, Inbred Lew
Rats, Inbred Strains
Receptors, Antigen, T-Cell, alpha-beta / metabolism
Receptors, Immunologic / metabolism*
Signal Transduction
Time Factors
Transplantation, Homologous
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD; 0/Antigens, CD2; 0/CD48 antigen; 0/Receptors, Antigen, T-Cell, alpha-beta; 0/Receptors, Immunologic

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