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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

机译：消耗多配聚糖4 + T淋巴细胞使用毒素轴承树突状细胞结合硫酸乙酰肝素蛋白依赖的整合素配：一种新的机遇处理激活的T细胞驱动的疾病

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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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Hideo Akiyoshi; Jin-Sung Chung; Mizuki Tomihari; Ponciano D. Cruz Jr.; Kiyoshi Ariizumi;
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年(卷),期 -1(184),7
年度 -1
页码 3554–3561
总页数 18
原文格式 PDF
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1. 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. [J] . Akiyoshi H, Chung JS, Tomihari M, The Journal of Immunology: Official Journal of the American Association of Immunologists . 2010,第7期

机译：使用带有毒素的树突状细胞相关的硫酸乙酰肝素蛋白聚糖依赖性整联蛋白配体来消耗syndecan-4 + T淋巴细胞：治疗活化T细胞驱动疾病的新机会。
2. Endothelial heparan sulfate controls chemokine presentation in recruitment of lymphocytes and dendritic cells to lymph nodes. [J] . Bao X, Moseman EA, Saito H, Immunity . 2010,第5期

机译：内皮普普丹硫酸盐对趋化因子呈对淋巴细胞和树突细胞募集到淋巴结。
3. GlyCAM-1, a physiologic ligand for L-selectin, activates beta 2 integrins on naive peripheral lymphocytes. [J] . S T Hwang, M S Singer, P A Giblin, The Journal of Experomental Medicine . 1996,第4期

机译：GlyCAM-1是L-选择素的生理配体，可激活幼稚外周淋巴细胞上的β2整合素。
4. Endothelial Heparan Sulfate Controls Chemokine Presentation in Recruitment of Lymphocytes and Dendritic Cells to Lymph Nodes [O] . Xingfeng Bao, E. Ashley Moseman, Hideo Saito, -1

机译：内皮细胞硫酸乙酰肝素控制趋化因子在演讲淋巴细胞的招聘和树突状细胞淋巴结
5. 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 [O] . Hideo Akiyoshi, Jin-Sung Chung, Mizuki Tomihari, 2010

机译：使用含有毒素的树突细胞相关的硫酸乙酰硫酸盐蛋白多糖依赖性整联蛋白配体：治疗活性T细胞驱动疾病的新机会

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

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