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    • 6. 发明授权
    • Ex-vivo priming for generating cytotoxic T lymphocytes specific for non-tumor antigens to treat autoimmune and allergic disease
    • 用于产生特异于非肿瘤抗原的细胞毒性T淋巴细胞用于治疗自身免疫性和过敏性疾病的体外引发
    • US08084256B2
    • 2011-12-27
    • US12887032
    • 2010-09-21
    • Zeling CaiMichael R. JacksonPer A. PetersonWei-Xing ShiYan KongJuli DeGraw
    • Zeling CaiMichael R. JacksonPer A. PetersonWei-Xing ShiYan KongJuli DeGraw
    • C12N5/00C12N5/02
    • A61K39/0008A61K2035/122C12N5/0636C12N2501/23C12N2501/51C12N2501/58C12N2502/50C12N2502/99
    • Cytotoxic T lymphocytes (CTLs) specific for antigenic peptides derived from IgE molecule can be generated in vitro by stimulating resting naive CD8 T cells with IgE peptides presented by artificial antigen presenting cells. The IgE specific CTLs lyse the target cells loaded with IgE peptides in vitro and inhibit antigen specific IgE response in vivo. In addition, adoptive transfer of the IgE specific CTL to an asthmatic mouse model can inhibit the development of lung inflammation and airway hypersensitivity. IgE specific CTL provides a treatment for allergic asthma and other IgE-mediated allergic diseases. Antigenic peptides identified from non-tumor self-antigens induce specific cytotoxic T lymphocyte (CTL) in vitro. The CTL induced by peptides identified from CD40L can kill activated CD4 T cells. In vitro generated CTL specific for CD40L inhibit CD4-dependent antibody responses of all isotypes in vivo. In contrast, CTL induced by antigenic peptides derived from IgE specifically inhibit IgE responses, and adoptive transfer of CD40L-specific CTL to NOD mice at early age delay the development of diabetes in NOD mice. In vitro generated CTL specific for non-tumor self-antigens expressed on activated CD4 T cells regulate immune responses in vivo.
    • 可以通过用人造抗原呈递细胞呈递的IgE肽刺激静息幼稚CD8T细胞在体外产生来自IgE分子的抗原肽特异性的细胞毒性T淋巴细胞(CTL)。 IgE特异性CTL在体外裂解装载有IgE肽的靶细胞,并在体内抑制抗原特异性IgE反应。 此外,将IgE特异性CTL过继转移至哮喘小鼠模型可以抑制肺部炎症和气道超敏反应的发展。 IgE特异性CTL提供过敏性哮喘和其他IgE介导的过敏性疾病的治疗。 从非肿瘤自身抗原鉴定的抗原肽在体外诱导特异性细胞毒性T淋巴细胞(CTL)。 由CD40L鉴定的肽诱导的CTL可以杀死活化的CD4T细胞。 体外产生的CD40L特异性CTL可抑制体内所有同种型的CD4依赖性抗体反应。 相比之下,来自IgE的抗原肽诱导的CTL特异性抑制IgE应答,CD40L特异性CTL过早转移到NOD小鼠早期延迟NOD小鼠的糖尿病发展。 在活化的CD4T细胞上表达的非肿瘤自身抗原的体外产生的CTL调节体内的免疫应答。