Cellular Adjuvant Properties, Direct Cytotoxicity of Re-differentiated Vα24 Invariant NKT-like Cells from Human Induced Pluripotent Stem Cells.
Cellular Adjuvant Properties, Direct Cytotoxicity of Re-differentiated Vα24 Invariant NKT-like Cells from Human Induced Pluripotent Stem Cells.
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DOI：
10.1016/j.stemcr.2016.01.005
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发表时间：
2016-02-09
影响因子：
5.9
通讯作者：
Kaneko S
中科院分区：
文献类型：
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作者：
Kitayama S;Zhang R;Liu TY;Ueda N;Iriguchi S;Yasui Y;Kawai Y;Tatsumi M;Hirai N;Mizoro Y;Iwama T;Watanabe A;Nakanishi M;Kuzushima K;Uemura Y;Kaneko S
Vα24 不变自然杀伤 T (iNKT) 细胞是参与广泛免疫反应调节的 T 淋巴细胞亚群。它们识别抗原呈递细胞上 CD1d 呈递的脂质抗原，并诱导先天性和适应性免疫反应，从而增强针对癌症的有效免疫力。相反，在许多癌症患者中观察到 iNKT 细胞数量和功能减少。为了恢复这些数字，我们将人类 iNKT 细胞重新编程为多能性，然后通过基于 IL-7/IL-15 的优化细胞因子组合在体外将其重新分化为再生 iNKT 细胞。再分化的 iNKT 细胞响应 α-半乳糖神经酰胺而表现出增殖和 IFN-γ 产生，诱导树突状细胞成熟和细胞毒性 T 淋巴细胞和 NK 细胞的下游激活，并表现出 NKG2D 和 DNAM-1 介导的针对癌细胞系的 NK 细胞样细胞毒性。再分化 iNKT 细胞的免疫学特征及其来自诱导多能干细胞的无限可用性提供了一种潜在有效的癌症免疫疗法。人 iNKT 细胞衍生的 iPSC 已在体外分化为 Vα24 iNKT 样细胞 再分化的 iNKT 样 (Re-iNKT) 细胞已在功能上恢复特性 Re-iNKT 细胞可作为佐剂激活抗原特异性 CTL 和 NK 细胞 Re-iNKT 细胞通过 NKG2D 和 DNAM-1 依赖性机制发挥细胞毒活性 Kaneko、Uemura 及其同事检查了功能由 iPS 细胞在体外诱导的 Vα24+ 人 iNKT 细胞。再分化的 iNKT 细胞表现出免疫佐剂特性，可通过刺激树突状细胞诱导癌症抗原特异性细胞毒性 T 细胞，并通过诱导 NKG2D 表达和增加 DNAM-1 活性对癌细胞产生直接细胞毒性。这些特征表明，再分化的 iNKT 细胞是抗癌新免疫疗法的潜在来源。
Vα24 invariant natural killer T (iNKT) cells are a subset of T lymphocytes implicated in the regulation of broad immune responses. They recognize lipid antigens presented by CD1d on antigen-presenting cells and induce both innate and adaptive immune responses, which enhance effective immunity against cancer. Conversely, reduced iNKT cell numbers and function have been observed in many patients with cancer. To recover these numbers, we reprogrammed human iNKT cells to pluripotency and then re-differentiated them into regenerated iNKT cells in vitro through an IL-7/IL-15-based optimized cytokine combination. The re-differentiated iNKT cells showed proliferation and IFN-γ production in response to α-galactosylceramide, induced dendritic cell maturation and downstream activation of both cytotoxic T lymphocytes and NK cells, and exhibited NKG2D- and DNAM-1-mediated NK cell-like cytotoxicity against cancer cell lines. The immunological features of re-differentiated iNKT cells and their unlimited availability from induced pluripotent stem cells offer a potentially effective immunotherapy against cancer. Human iNKT cell-derived iPSCs have differentiated into Vα24 iNKT-like cells in vitro Re-differentiated iNKT-like (Re-iNKT) cells have functionally recovered properties Re-iNKT cells function as an adjuvant to activate antigen-specific CTLs and NK cells Re-iNKT cells exert cytotoxic activity via NKG2D- and DNAM-1-dependent mechanism Kaneko, Uemura, and colleagues examined functional Vα24+ human iNKT cells induced from iPS cells in vitro. The re-differentiated iNKT cells demonstrated immune-adjuvant properties to induce cancer antigen-specific cytotoxic T cells via dendritic cell stimulation and direct cytotoxicity to cancer cells by induced NKG2D expression and increased DNAM-1 activity. These features indicate that re-differentiated iNKT cells are a potential source for new immunotherapies against cancer.