肝脏定向 AAV 基因疗法后 CD8+ 调节性 T 细胞的上调

IF 3.7 4区 医学 Q2 CELL BIOLOGY
Cristina D. Gaddie , Kevin G. Senior , Christopher Chan , Brad E. Hoffman , Geoffrey D. Keeler
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引用次数: 0

摘要

肝脏定向 AAV 基因疗法是一种治疗多种疾病的独特方法。这部分是由于诱导了对转基因产品的耐受性。尽管人体内有大量公认的调节细胞,但目前缺乏文献支持肝脏 AAV 基因转移后诱导出非 CD4+ 调节细胞。在这项研究中,我们发现小鼠的 PBMCs 在服用仅有外壳的 AAV 和治疗性转基因 AAV 后,CD8+调节性 T 细胞会上调。此外,我们还证明了肝脏 AAV 基因转移会导致实验性自身免疫性脑脊髓炎诱导的 CD8+ 调节性 T 细胞显著增加。值得注意的是,这种反应只发生在治疗载体处理过的动物身上,而不是仅有囊壳的对照组。了解这些细胞在治疗效果中的作用,将有助于开发出能充分利用体内各种调节细胞的改良型 AAV 载体。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Upregulation of CD8+ regulatory T cells following liver-directed AAV gene therapy

Upregulation of CD8+ regulatory T cells following liver-directed AAV gene therapy

Upregulation of CD8+ regulatory T cells following liver-directed AAV gene therapy

Liver-directed AAV gene therapy represents a unique treatment modality for a host of diseases. This is due, in part, to the induction of tolerance to transgene products. Despite the plethora of recognized regulatory cells in the body, there is currently a lack of literature supporting the induction of non-CD4+ regulatory cells following hepatic AAV gene transfer. In this work, we show that CD8+ regulatory T cells are up-regulated in PBMCs of mice following capsid only and therapeutic transgene AAV administration. Further, we demonstrate that hepatic AAV gene transfer results in a significant increase in CD8+ regulatory T cells following experimental autoimmune encephalomyelitis induction. Notably, this response occurred only in therapeutic vector treated animals, not capsid only controls. Understanding the role these cells play in treatment efficacy will result in the development of improved AAV vectors that take advantage of the full gamut of regulatory cells within the body.

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来源期刊
Cellular immunology
Cellular immunology 生物-免疫学
CiteScore
8.20
自引率
2.30%
发文量
102
审稿时长
30 days
期刊介绍: Cellular Immunology publishes original investigations concerned with the immunological activities of cells in experimental or clinical situations. The scope of the journal encompasses the broad area of in vitro and in vivo studies of cellular immune responses. Purely clinical descriptive studies are not considered. Research Areas include: • Antigen receptor sites • Autoimmunity • Delayed-type hypersensitivity or cellular immunity • Immunologic deficiency states and their reconstitution • Immunologic surveillance and tumor immunity • Immunomodulation • Immunotherapy • Lymphokines and cytokines • Nonantibody immunity • Parasite immunology • Resistance to intracellular microbial and viral infection • Thymus and lymphocyte immunobiology • Transplantation immunology • Tumor immunity.
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