Document Detail


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.
MedLine Citation:
PMID:  21252093     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Jin-Sung Chung; Lisa H Shiue; Madeleine Duvic; Amit Pandya; Ponciano D Cruz; Kiyoshi Ariizumi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-01-20
Journal Detail:
Title:  Blood     Volume:  117     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-25     Completed Date:  2011-06-06     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3382-90     Citation Subset:  AIM; IM    
Affiliation:
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.
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MeSH Terms
Descriptor/Qualifier:
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:
AI064927-05/AI/NIAID NIH HHS; R01 AI064927-05A2/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/GPNMB protein, human; 0/Membrane Glycoproteins; 0/Receptors, Immunologic; 0/Syndecan-4; 0/Transforming Growth Factor beta; 9050-30-0/Heparitin Sulfate
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