Depleting syndecan-4+ T lymphocytes using toxin-bearing dendritic cell-associated heparan sulfate proteoglycan-dependent integrin ligand: A new opportunity for treating activated T cell-driven disease

Hideo Akiyoshi, Jin Sung Chung, Mizuki Tomihari, Ponciano D Cruz, Kiyoshi Ariizumi

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Because syndecan-4 (SD-4) is expressed by some (but not all) T cells following activation and serves as the exclusive ligand of dendritic cell-associated heparan sulfate proteoglycan-dependent integrin ligand (DC-HIL), we envisioned the DC-HIL/SD-4 pathway to be a therapeutic target for conditions mediated by selectively activated T cells. We conjugated soluble DC-HIL receptor with the toxin saporin (SAP; DC-HIL-SAP) and showed it to bind activated (but not resting) T cells and become internalized by and deplete SD-4+ T cells. In hapten-sensitized mice, DC-HIL-SAP injected i.v. prior to hapten challenge led to markedly suppressed contact hypersensitivity responses that lasted 3 wk and were restricted to the hapten to which the mice were originally sensitized. Such suppression was not observed when DC-HIL-SAP was applied during sensitization. Moreover, the same infusion of DC-HIL-SAP produced almost complete disappearance of SD-4+ cells in haptenated skin and a 40% reduction of such cells within draining lymph nodes. Our results provide a strong rationale for exploring use of toxin-conjugated DC-HIL to treat activated T cell-driven disease in humans.

Original languageEnglish (US)
Pages (from-to)3554-3561
Number of pages8
JournalJournal of Immunology
Volume184
Issue number7
DOIs
StatePublished - Apr 1 2010

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Syndecan-4
Heparan Sulfate Proteoglycans
Integrins
Dendritic Cells
Haptens
Ligands
T-Lymphocytes
Contact Dermatitis
Lymph Nodes
Skin

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

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title = "Depleting syndecan-4+ T lymphocytes using toxin-bearing dendritic cell-associated heparan sulfate proteoglycan-dependent integrin ligand: A new opportunity for treating activated T cell-driven disease",
abstract = "Because syndecan-4 (SD-4) is expressed by some (but not all) T cells following activation and serves as the exclusive ligand of dendritic cell-associated heparan sulfate proteoglycan-dependent integrin ligand (DC-HIL), we envisioned the DC-HIL/SD-4 pathway to be a therapeutic target for conditions mediated by selectively activated T cells. We conjugated soluble DC-HIL receptor with the toxin saporin (SAP; DC-HIL-SAP) and showed it to bind activated (but not resting) T cells and become internalized by and deplete SD-4+ T cells. In hapten-sensitized mice, DC-HIL-SAP injected i.v. prior to hapten challenge led to markedly suppressed contact hypersensitivity responses that lasted 3 wk and were restricted to the hapten to which the mice were originally sensitized. Such suppression was not observed when DC-HIL-SAP was applied during sensitization. Moreover, the same infusion of DC-HIL-SAP produced almost complete disappearance of SD-4+ cells in haptenated skin and a 40{\%} reduction of such cells within draining lymph nodes. Our results provide a strong rationale for exploring use of toxin-conjugated DC-HIL to treat activated T cell-driven disease in humans.",
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AU - Chung, Jin Sung

AU - Tomihari, Mizuki

AU - Cruz, Ponciano D

AU - Ariizumi, Kiyoshi

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