Abstract
Receptor crosslinking of T-cell hybridomas induces cell activation followed by apoptosis. This activation-induced cell death requires de novo synthesis of RNA and proteins, but the actual gene products that provide the death signal have not been identified. We show here that receptor crosslinking induces Fas ligand and upregulates Fas, and that the ensuing engagement of Fas by Fas ligand activates the cell-death programme. Cell death, but not activation, can be selectively prevented by a soluble Fas-immunoglobulin fusion protein. Thus, Fas and Fas ligand are the death-gene products, and their interaction accounts for the molecular mechanism of activation-induced T-cell death.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Animals
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Antigens, Surface / genetics
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Antigens, Surface / physiology*
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Apoptosis / physiology*
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Base Sequence
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DNA
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Fas Ligand Protein
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Humans
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Hybridomas
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Immunoglobulin G / genetics
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Lymphocyte Activation*
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology*
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Mice
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Molecular Sequence Data
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RNA, Messenger / metabolism
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Recombinant Fusion Proteins
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T-Lymphocytes / immunology
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T-Lymphocytes / physiology*
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fas Receptor
Substances
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Antigens, Surface
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FASLG protein, human
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Fas Ligand Protein
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Fasl protein, mouse
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Immunoglobulin G
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Membrane Glycoproteins
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RNA, Messenger
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Recombinant Fusion Proteins
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fas Receptor
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DNA