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OT-I TCR 转基因小鼠用于研究 PTPN22 在抗癌免疫中的作用

英文原题:OT-I TCR Transgenic Mice to Study the Role of PTPN22 in Anti-cancer Immunity.

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OT-I TCR Transgenic Mice to Study the Role of PTPN22 in Anti-cancer Immunity.

PubMed 2024/01/01(内容时间) Methods Mol Biol

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中文摘要

蛋白酪氨酸磷酸酶非受体22型(PTPN22)是免疫细胞活化和反应的关键调节因子。PTPN22的遗传多态性与自身免疫性疾病发病风险增加密切相关,而对PTPN22缺陷小鼠品系的分析已确定PTPN22是T细胞抗原受体信号传导的负调节因子。除了在维持免疫耐受中的这些关键作用外,PTPN22还作为T细胞抗肿瘤反应的细胞内检查点,提示PTPN22可能是改善T细胞免疫治疗的有用靶点。为评估靶向PTPN22的潜力,我们将Ptpn22缺陷小鼠与OT-I TCR转基因背景杂交,并在小鼠肿瘤模型中采用过继性T细胞转移方法。我们提供了用于体外扩增效应OT-I细胞毒性T淋巴细胞的 basic 方法、体外表型分析以及体内过继性T细胞转移模型,以评估PTPN22在抗肿瘤免疫中的作用。

展开英文摘要原文

Phosphotyrosine phosphatase non-receptor type 22 (PTPN22) is a key regulator of immune cell activation and responses. Genetic polymorphisms of PTPN22 have been strongly linked with an increased risk of developing autoimmune diseases, while analysis of PTPN22-deficient mouse strains has determined that PTPN22 serves as a negative regulator of T cell antigen receptor signaling.

As well as these key roles in maintaining immune tolerance, PTPN22 acts as an intracellular checkpoint for T cell responses to cancer, suggesting that PTPN22 might be a useful target to improve T cell immunotherapies. To assess the potential for targeting PTPN22, we have crossed Ptpn22-deficient mice to an OT-I TCR transgenic background and used adoptive T cell transfer approaches in mouse cancer models.

We provide basic methods for the in vitro expansion of effector OT-I cytotoxic T lymphocytes, in vitro phenotypic analysis, and in vivo adoptive T cell transfer models to assess the role of PTPN22 in anti-cancer immunity.

论文信息

作者
Brownlie RJ、Zamoyska R、Salmond RJ
第一作者单位
Leeds Institute of Medical Research at St James's, University of Leeds, Wellcome Trust Brenner Building, St James's University Hospital, Leeds, UK.United Kingdom
通讯作者单位
Leeds Institute of Medical Research at St James's, University of Leeds, Wellcome Trust Brenner Building, St James's University Hospital, Leeds, UK. r.j.salmond@leeds.ac.uk.United Kingdom
期刊
Methods in molecular biology (Clifton, N.J.)2024
原文标识
PubMed 38147209 · DOI 10.1007/978-1-0716-3569-8_5