Leeds Institute of Medical Research at St James's, University of Leeds, Wellcome Trust Brenner Building, St James's University Hospital, Leeds, UK.
Institute of Immunology and Infection Research, University of Edinburgh, Ashworth Laboratories, Edinburgh, UK.
Methods Mol Biol. 2024;2743:81-92. doi: 10.1007/978-1-0716-3569-8_5.
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.
磷酸酪氨酸磷酸酶非受体型 22（PTPN22）是免疫细胞激活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的风险增加密切相关，而对 PTPN22 缺陷型小鼠品系的分析表明，PTPN22 作为 T 细胞抗原受体信号的负调节剂。除了在维持免疫耐受方面的这些关键作用外，PTPN22 还是 T 细胞对癌症反应的细胞内检查点，这表明 PTPN22 可能是改善 T 细胞免疫疗法的有用靶点。为了评估靶向 PTPN22 的潜力，我们将 Ptpn22 缺陷型小鼠与 OT-I TCR 转基因背景进行了杂交，并在小鼠癌症模型中使用了过继性 T 细胞转移方法。我们提供了体外扩增效应 OT-I 细胞毒性 T 淋巴细胞、体外表型分析以及体内过继性 T 细胞转移模型的基本方法，以评估 PTPN22 在抗癌免疫中的作用。
