Abstract
Human Treg and Th clones secrete the latent form of TGF-beta, in which the mature TGF-beta protein is bound to the latency-associated peptide (LAP), and is thereby prevented from binding to the TGF-beta receptor. We previously showed that upon TCR stimulation, human Treg clones but not Th clones produce active TGF-beta and bear LAP on their surface. Here, we show that latent TGF-beta, i.e. both LAP and mature TGF-beta, binds to glycoprotein A repetitions predominant (GARP), a transmembrane protein containing leucine rich repeats, which is present on the surface of stimulated Treg clones but not on Th clones. Membrane localization of latent TGF-beta mediated by binding to GARP may be necessary for the ability of Treg to activate TGF-beta upon TCR stimulation. However, it is not sufficient as lentiviral-mediated expression of GARP in human Th cells induces binding of latent TGF-beta to the cell surface, but does not result in the production of active TGF-beta upon stimulation of these Th cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blotting, Western
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CD4 Antigens / metabolism
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Cell Membrane / metabolism*
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Cells, Cultured
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Flow Cytometry
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Humans
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Interleukin-2 Receptor alpha Subunit / metabolism
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Interleukin-7 Receptor alpha Subunit / metabolism
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Jurkat Cells
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Latent TGF-beta Binding Proteins / genetics
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Latent TGF-beta Binding Proteins / metabolism
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Lymphocyte Activation / immunology
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Models, Biological
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Muromonab-CD3 / immunology
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Protein Binding
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Reverse Transcriptase Polymerase Chain Reaction
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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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T-Lymphocytes, Regulatory / cytology
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / metabolism*
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / metabolism*
Substances
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CD4 Antigens
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Interleukin-2 Receptor alpha Subunit
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Interleukin-7 Receptor alpha Subunit
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LRRC32 protein, human
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Latent TGF-beta Binding Proteins
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Membrane Proteins
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Muromonab-CD3
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Transforming Growth Factor beta