Sézary syndrome cells overexpress syndecan-4 bearing distinct heparan sulfate moieties that suppress T-cell activation by binding DC-HIL and trapping TGF-β on the cell surface
Blood, ISSN: 0006-4971, Vol: 117, Issue: 12, Page: 3382-3390
2011
- 31Citations
- 35Captures
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Metrics Details
- Citations31
- Citation Indexes31
- 31
- CrossRef26
- Captures35
- Readers35
- 35
Article Description
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.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0006497120365034; http://dx.doi.org/10.1182/blood-2010-08-302034; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=79953075757&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/21252093; https://ashpublications.org/blood/article/117/12/3382/20455/S%C3%A9zary-syndrome-cells-overexpress-syndecan4
American Society of Hematology
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