Departamento de Biologia, Facultad de Ciencias, Universidad de Chile, Santiago, Chile.
Facultad de Medicina, Universidad San Sebastian, Santiago, Chile.
Front Immunol. 2018 Feb 8;9:209. doi: 10.3389/fimmu.2018.00209. eCollection 2018.
Memory CD8 T cells are ideal candidates for cancer immunotherapy because they can mediate long-term protection against tumors. However, the therapeutic potential of different -generated CD8 T cell effector subsets to persist and become memory cells has not been fully characterized. Type 1 CD8 T (Tc1) cells produce interferon-γ and are endowed with high cytotoxic capacity, whereas IL-17-producing CD8 T (Tc17) cells are less cytotoxic but display enhanced self-renewal capacity. We sought to evaluate the functional properties of -generated Tc17 cells and elucidate their potential to become long lasting memory cells. Our results show that -generated Tc17 cells display a greater persistence and expansion in response to secondary antigen stimulation compared to Tc1 cells. When transferred into recipient mice, Tc17 cells persist in secondary lymphoid organs, present a recirculation behavior consistent with central memory T cells, and can shift to a Tc1 phenotype. Accordingly, Tc17 cells are endowed with a higher mitochondrial spare respiratory capacity than Tc1 cells and express higher levels of memory-related molecules than Tc1 cells. Together, these results demonstrate that -generated Tc17 cells acquire a central memory program and provide a lasting reservoir of Tc1 cells , thus supporting the use of Tc17 lymphocytes in the design of novel and more effective therapies.
记忆性 CD8 T 细胞是癌症免疫治疗的理想候选者,因为它们可以介导对肿瘤的长期保护。然而,不同分化生成的 CD8 T 细胞效应亚群持续存在并成为记忆细胞的治疗潜力尚未得到充分表征。1 型 CD8 T(Tc1)细胞产生干扰素-γ,具有高细胞毒性能力,而产生白细胞介素-17 的 CD8 T(Tc17)细胞细胞毒性较低,但显示出增强的自我更新能力。我们试图评估-生成的 Tc17 细胞的功能特性,并阐明它们成为持久记忆细胞的潜力。我们的结果表明,与 Tc1 细胞相比,-生成的 Tc17 细胞在二次抗原刺激下表现出更大的持久性和扩增。当转移到受体小鼠中时,Tc17 细胞在次级淋巴器官中持续存在,表现出与中央记忆 T 细胞一致的再循环行为,并可以向 Tc1 表型转变。因此,Tc17 细胞比 Tc1 细胞具有更高的线粒体备用呼吸能力,并表达更高水平的记忆相关分子。总之,这些结果表明,-生成的 Tc17 细胞获得了中央记忆程序,并提供了持久的 Tc1 细胞储备,从而支持在设计新型更有效的治疗方法中使用 Tc17 淋巴细胞。