Abstract
The newly identified TIM family of proteins is associated with regulation of T helper type 1 (T(H)1) and T(H)2 immune responses. TIM-1 is genetically linked to asthma and is a receptor for hepatitis A virus, but the endogenous ligand of TIM-1 is not known. Here we show that TIM-4, which is expressed by antigen-presenting cells, is the ligand for TIM-1. In vivo administration of either soluble TIM-1-immunoglobulin (TIM-1-Ig) fusion protein or TIM-4-Ig fusion protein resulted in hyperproliferation of T cells, and TIM-4-Ig costimulated T cell proliferation mediated by CD3 and CD28 in vitro. These data suggest that the TIM-1-TIM-4 interaction is involved in regulating T cell proliferation.
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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Animals
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Antigen Presentation
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Antigen-Presenting Cells / immunology
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Antigen-Presenting Cells / metabolism
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Cell Proliferation / drug effects
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Cricetinae
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Female
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Hepatitis A Virus Cellular Receptor 1
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Humans
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Immunoglobulins / pharmacology
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Ligands
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Membrane Proteins / immunology
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Membrane Proteins / isolation & purification
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Membrane Proteins / metabolism*
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Membrane Proteins / pharmacology
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Mice
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Protein Binding
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T-Lymphocytes / cytology*
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
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Th2 Cells / drug effects
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Th2 Cells / immunology
Substances
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Havcr1 protein, mouse
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Hepatitis A Virus Cellular Receptor 1
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Immunoglobulins
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Ligands
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Membrane Proteins
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TIM-4 protein, mouse