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首页> 外文期刊>Gene Therapy and Molecular Biology >Cytokine gene transduced T cells in the treatment ofallergic encephalomyelitis and airwayhypersensitivity
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Cytokine gene transduced T cells in the treatment ofallergic encephalomyelitis and airwayhypersensitivity

机译:细胞因子基因转导的T细胞治疗过敏性脑脊髓炎和气道超敏反应

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SummaryTGF-β1 or IL-10 transduced myelin basic protein (MBP)-specific BALB/c cloned Th1 cells were injected into SJL x BALB/c F1 mice 11-15 days after immunization with proteolipid protein to induce EAE. TGF-β1/MBP T cells significantly ameliorated the EAE, while IL-10/MBP T cells were less effective. TGF-β1 transduced ovalbumin (OVA)-specific Th1 clones did not influence EAE, even when re-activated by OVA in vivo. However, TGF-β1/OVA T cells did protect against OVA-specific Th2-cell mediated airway hyper-reactivity induced by inhaled OVA. TGF- β1/KLH T cells did not prevent OVA-induced airway hyper-reactivity in mice sensitized and challenged with OVA alone, but did protect mice challenged with KLH + OVA. Thus, the antigen specificity of the Th1 cells allows site- specific delivery of therapeutic TGF-β1 to both Th1 and Th2 cell-mediated inflammatory infiltrates. EAE relapses, induced by bacterial superantigen or endotoxin within 2 weeks, but not >6 weeks, after transfer of TGF-β1 or IL- 10/MBP T cells, were reduced. Relapses induced 5 weeks after immunization with PLP could be prevented by simultaneously injected TGF-β1/MBP cells. Spinal cords taken 12-50 days after TGF-β1/MBP cells contained TGF- β1 cDNA. Spinal cords from the majority of mice receiving IL-10/MBP cells contained IL-10 cDNA up to 2 weeks, but not 50 days after cell transfer. Thus, TGF-β1-transduced T cells may be useful in the therapy of autoimmune and allergic inflammatory diseases, but in the EAE model, the same approach with IL-10-transduced T cells appears less effective.
机译:总结在用蛋白脂蛋白免疫诱导EAE后11-15天,将TGF-β1或IL-10转导的髓磷脂碱性蛋白(MBP)特异性BALB / c克隆的Th1细胞注射到SJL x BALB / c F1小鼠中。 TGF-β1/ MBP T细胞显着改善了EAE,而IL-10 / MBP T细胞效果较差。 TGF-β1转导的卵清蛋白(OVA)特异性Th1克隆即使在体内被OVA重新激活也不会影响EAE。然而,TGF-β1/ OVA T细胞确实可以抵抗OVA特异性Th2细胞介导的吸入OVA诱导的气道高反应性。 TGF-β1/ KLH T细胞不能预防仅用OVA致敏和攻击的小鼠的OVA诱导的气道高反应性,但可以保护用KLH + OVA攻击的小鼠。因此,Th1细胞的抗原特异性允许治疗性TGF-β1向Th1和Th2细胞介导的炎性浸润物的位点特异性递送。 TGF-β1或IL-10 / MBP T细胞转移后,细菌超抗原或内毒素诱导的EAE复发在2周内(但不> 6周)降低。同时注射TGF-β1/ MBP细胞可以预防PLP免疫5周后诱导的复发。 TGF-β1/ MBP细胞后12-50天取出的脊髓含有TGF-β1cDNA。来自大多数接受IL-10 / MBP细胞的小鼠的脊髓在细胞转移后长达2周而不是50天后仍含有IL-10 cDNA。因此,TGF-β1转导的T细胞可用于自身免疫和过敏性炎症疾病的治疗,但在EAE模型中,IL-10转导的T细胞的相同方法似乎效果较差。

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