首页> 外国专利> EX-VIVO PRIMING FOR GENERATING CYTOTOXIC T LYMPHOCYTES SPECIFIC FOR NON-TUMOR ANTIGENS TO TREAT AUTOIMMUNE AND ALLERGIC DISEASE

EX-VIVO PRIMING FOR GENERATING CYTOTOXIC T LYMPHOCYTES SPECIFIC FOR NON-TUMOR ANTIGENS TO TREAT AUTOIMMUNE AND ALLERGIC DISEASE

机译:用于产生非肿瘤抗原特异性的细胞毒性T淋巴细胞的体外制备,以治疗自身免疫性疾病和过敏性疾病

摘要

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.
机译:通过用人工抗原呈递细胞呈递的IgE肽刺激静息的幼稚CD8 T细胞,可在体外产生对源自IgE分子的抗原肽具有特异性的细胞毒性T淋巴细胞(CTL)。 IgE特异的CTL在体外裂解装有IgE肽的靶细胞,并在体内抑制抗原特异性IgE应答。此外,将IgE特异性CTL过继转移至哮喘小鼠模型可抑制肺部炎症和气道超敏反应的发展。 IgE特异性CTL为过敏性哮喘和其他IgE介导的过敏性疾病提供治疗。从非肿瘤自身抗原中鉴定出的抗原肽可在体外诱导特异性细胞毒性T淋巴细胞(CTL)。由CD40L鉴定出的肽诱导的CTL可以杀死活化的CD4 T细胞。体外产生的对CD40L特异的CTL在体内抑制所有同种型的CD4依赖性抗体应答。相反,由IgE衍生的抗原肽诱导的CTL特异性抑制IgE反应,CD40L特异性CTL过早转移至NOD小鼠会延缓NOD小鼠糖尿病的发展。体外产生的,对活化的CD4 T细胞上表达的非肿瘤自身抗原具有特异性的CTL调节体内的免疫反应。

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