Document Detail

CD40.FasL inhibits human T cells: evidence for an auto-inhibitory loop-back mechanism.
MedLine Citation:
PMID:  17314083     Owner:  NLM     Status:  MEDLINE    
A chimeric CD40.FasL (CD40-CD95L) protein was designed with the combined capacities to bind to two surface receptors on activated T cells, CD40 ligand (CD40L; CD154) and Fas receptor (CD95). CD40.FasL, once tethered to the cell surface via one of its ends, can transmit a signal via its other end. In principle, simultaneous triggering from both ends is possible, and thus there is the intriguing potential for 'auto-inhibition' if such dual triggering occurs on the same cell itself. Several lines of evidence support this mechanism: (i) CD40.FasL is cytotoxic to Fas receptor-positive cell lines of different cell lineages, (ii) CD40.FasL's function is potentiated when there is enforced expression of CD40L on target cells, (iii) CD40.FasL inhibition does not require intercellular contact, as demonstrated by soft agar clone formation and cell dilution analysis and (iv) introduction of exogenous CD40 into the system interferes with CD40.FasL inhibition. Taken together, these data are consistent with a 'loop-back' inhibitory mechanism within individual activated (CD40L and Fas receptor expressing) T cells causing suicide of these T cells. Significantly, this type of fusion protein provides a unique way to confine immunoinhibition to activated T cells.
M Dranitzki-Elhalel; J H Huang; M Sasson; J Rachmilewitz; M Parnas; M L Tykocinski
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-02-20
Journal Detail:
Title:  International immunology     Volume:  19     ISSN:  0953-8178     ISO Abbreviation:  Int. Immunol.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-03-30     Completed Date:  2007-08-27     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  8916182     Medline TA:  Int Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  355-63     Citation Subset:  IM    
Nephrology and Hypertension Services, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
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MeSH Terms
Antibodies, Monoclonal / immunology,  pharmacology
Antigens, CD3 / immunology
Antigens, CD40 / genetics*,  metabolism
Antigens, CD8 / genetics,  metabolism
Antigens, CD95 / metabolism
Apoptosis / drug effects*
B-Lymphocytes / cytology,  drug effects,  metabolism
CD40 Ligand / genetics,  metabolism
Cell Line
Cell Line, Tumor
Cell Proliferation / drug effects
Coculture Techniques
Dose-Response Relationship, Drug
Fas Ligand Protein / genetics*,  metabolism
Jurkat Cells
Leukocytes, Mononuclear / cytology,  drug effects,  metabolism
Lymphocyte Activation / drug effects,  immunology
NIH 3T3 Cells
Protein Binding / drug effects
Recombinant Fusion Proteins / metabolism,  pharmacology*
T-Lymphocytes / cytology,  drug effects*,  metabolism
Grant Support
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD3; 0/Antigens, CD40; 0/Antigens, CD8; 0/Antigens, CD95; 0/Fas Ligand Protein; 0/Recombinant Fusion Proteins; 147205-72-9/CD40 Ligand

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