| Sézary syndrome cells overexpress syndecan-4 bearing distinct heparan sulfate moieties that suppress T-cell activation by binding DC-HIL and trapping TGF-beta on the cell surface. | |
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MedLine Citation:
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PMID: 21252093 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Because syndecan-4 (SD-4) on effector and memory T cells inhibits T-cell activation by binding dendritic cell-associated heparan sulfate proteoglycan-integrin ligand (DC-HIL) on antigen presenting cells and because malignant cells of the cutaneous T-cell lymphoma (CTCL) subset, Sézary syndrome (SS), exhibit memory T-cell phenotype, we posited SS cells to express SD-4. Indeed, malignant T cells from patients with SS and from CTCL cell lines constitutively expressed SD-4 at high levels, in contrast to T cells from healthy volunteers and patients with other inflammatory skin diseases and to non-CTCL cell lines that did not. SS cells also bound to DC-HIL at a level higher than normal T cells activated in vitro, resulting in their inhibited proliferation to anti-CD3 antibody. SD-4 on SS cells also trapped transforming growth factor-β1 to their cell surface, enhancing their ability to inhibit activation of syngeneic and allogeneic normal T cells. All of these inhibitory properties were dependent on overexpression of distinct heparan sulfate (HS) moieties by SD-4 on SS cells. Finally, we showed toxin-conjugated DC-HIL to abrogate the ability of SS cells to proliferate in vitro. These findings indicate that SD-4 bearing distinct HS moieties plays a pathogenic role in SS and may be targeted for treatment. |
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Authors:
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Jin-Sung Chung; Lisa H Shiue; Madeleine Duvic; Amit Pandya; Ponciano D Cruz; Kiyoshi Ariizumi |
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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: 2011-01-20 |
Journal Detail:
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Title: Blood Volume: 117 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-03-25 Completed Date: 2011-06-06 Revised Date: 2012-09-18 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 3382-90 Citation Subset: AIM; IM |
Affiliation:
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Department of Dermatology, The University of Texas Southwestern Medical Center and Dermatology Section (Medical Service), Dallas Veterans Affairs Medical Center, Dallas, TX 75390-9069, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged Aged, 80 and over Cell Membrane / metabolism Female Heparitin Sulfate / chemistry, immunology, metabolism, physiology* Humans Lymphocyte Activation / immunology* Lymphoma, T-Cell, Cutaneous / immunology, metabolism, pathology Male Membrane Glycoproteins / metabolism*, physiology Middle Aged Protein Binding / immunology, physiology Protein Transport Receptors, Immunologic / immunology, metabolism* Sezary Syndrome / genetics, immunology*, metabolism, pathology Syndecan-4 / chemistry, genetics*, metabolism T-Lymphocytes / immunology*, metabolism, pathology Transforming Growth Factor beta / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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AI064927-05/AI/NIAID NIH HHS; R01 AI064927-05A2/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/GPNMB protein, human; 0/Membrane Glycoproteins; 0/Receptors, Immunologic; 0/Syndecan-4; 0/Transforming Growth Factor beta; 9050-30-0/Heparitin Sulfate |
| Comments/Corrections | |
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