Sim Ji Hyun, Kim Jin-Hee, Park Ae Kyung, Lee Jeeyun, Kim Kyoung-Mee, Shin Hyun Mu, Kim Minji, Choi Kyungho, Choi Eun Young, Kang Insoo, Lee Dong-Sup, Kim Hang-Rae
Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
Medical Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
J Immunol. 2020 Dec 1;205(11):2968-2978. doi: 10.4049/jimmunol.1901470. Epub 2020 Oct 26.
Effector memory (EM) CD8 T cells expressing lower levels of IL-7R α (IL-7Rα) from healthy individuals are partly compromised in vitro, but the identity of these cells has remained unclear. In this study, we demonstrate that human IL-7Rα EM CD8 T cells are naturally occurring anergic cells in vivo and impaired in proliferation and IL-2 production but competent in IFN-γ and TNF-α production, a state that can be restored by IL-2 stimulation. IL-7Rα EM CD8 T cells show decreased expression of GATA3 and c-MYC and are defective in metabolic reprogramming toward glycolysis, a process required for the proliferation of T cells. However, IL-7Rα EM CD8 T cells can proliferate with TCR stimulation in the presence of IL-2 and IL-15, suggesting that these cells can be restored to normality or increased activity by inflammatory conditions and may serve as a reservoir for functional immunity.
来自健康个体的表达较低水平白细胞介素-7受体α（IL-7Rα）的效应记忆（EM）CD8 T细胞在体外功能部分受损，但其细胞特性仍不明确。在本研究中，我们证明人类IL-7Rα EM CD8 T细胞在体内是天然存在的无反应性细胞，其增殖和白细胞介素-2产生受损，但干扰素-γ和肿瘤坏死因子-α产生功能正常，这种状态可通过白细胞介素-2刺激得以恢复。IL-7Rα EM CD8 T细胞显示GATA3和c-MYC表达降低，且在向糖酵解的代谢重编程方面存在缺陷，而糖酵解是T细胞增殖所需的过程。然而，IL-7Rα EM CD8 T细胞在存在白细胞介素-2和白细胞介素-15的情况下可通过TCR刺激而增殖，这表明这些细胞可通过炎症条件恢复正常或增强活性，并可能作为功能性免疫的储备细胞。
