| CD40.FasL inhibits human T cells: evidence for an auto-inhibitory loop-back mechanism. | |
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MedLine Citation:
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PMID: 17314083 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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M Dranitzki-Elhalel; J H Huang; M Sasson; J Rachmilewitz; M Parnas; M L Tykocinski |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2007-02-20 |
Journal Detail:
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Title: International immunology Volume: 19 ISSN: 0953-8178 ISO Abbreviation: Int. Immunol. Publication Date: 2007 Apr |
Date Detail:
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Created Date: 2007-03-30 Completed Date: 2007-08-27 Revised Date: 2007-12-03 |
Medline Journal Info:
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Nlm Unique ID: 8916182 Medline TA: Int Immunol Country: England |
Other Details:
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Languages: eng Pagination: 355-63 Citation Subset: IM |
Affiliation:
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Nephrology and Hypertension Services, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. michalelhalel@gmail.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals 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 Humans Jurkat Cells Leukocytes, Mononuclear / cytology, drug effects, metabolism Lymphocyte Activation / drug effects, immunology Mice NIH 3T3 Cells Protein Binding / drug effects Recombinant Fusion Proteins / metabolism, pharmacology* T-Lymphocytes / cytology, drug effects*, metabolism Transfection |
| Grant Support | |
ID/Acronym/Agency:
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AI31044-11/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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