Pokhrel Srijana, Jones Devin M, Leonard Melissa R, Tuazon Jasmine A, Read Kaitlin A, Dileepan Gayathri, Warren Robert T, Gong Qiaoke, Yount Jacob S, Xin Gang, Forero Adriana, Ghoneim Hazem E, Collins Patrick L, Hemann Emily A, Oestreich Kenneth J
Department of Microbial Infection and Immunity; The Ohio State University College of Medicine and Wexner Medical Center, Columbus, Ohio, 43210; USA.
Biomedical Sciences Graduate Program, The Ohio State University College of Medicine, Columbus, OH, 43210; USA.
bioRxiv. 2025 Jun 16:2025.06.11.659122. doi: 10.1101/2025.06.11.659122.
CD8 virtual memory T (T) cells are memory-like cells that rapidly respond to infection via antigen-independent bystander effector functions. While it is recognized that T cells arise independently of foreign antigen encounter, the mechanisms governing their development are not fully understood. Here, we identify the transcription factor Aiolos as a negative regulator of T cells. We observed higher quantities of T cells in the spleens of uninfected Aiolos-deficient ( ) mice relative to wild-type (WT). Furthermore, T cells produced higher levels of IFN-γ and granzyme B. In addition, we found that T cells accumulated to higher quantities in the lungs within 24 hours of influenza virus infection. In line with enhanced T functional capacity and lung trafficking, Aiolos-deficient mice cleared virus more rapidly and exhibited reduced morbidity relative to WT animals. Mechanistically, we observed that Aiolos represses the T transcriptional regulator Eomes and the IL-15R subunit CD122 (IL-15Rβ/IL-2Rβ), known contributors of T cell generation. Collectively, these findings establish Aiolos as a novel molecular repressor of T generation and function.
CD8 虚拟记忆性 T（T）细胞是一类记忆样细胞，可通过不依赖抗原的旁观者效应功能对感染迅速做出反应。虽然人们认识到 T 细胞独立于接触外来抗原而产生，但其发育调控机制尚未完全明确。在此，我们确定转录因子艾奥洛斯（Aiolos）是 T 细胞的负调节因子。我们观察到，与野生型（WT）小鼠相比，未感染的艾奥洛斯缺陷型（ ）小鼠脾脏中的 T 细胞数量更多。此外，T 细胞产生的干扰素-γ（IFN-γ）和颗粒酶 B 水平更高。另外，我们发现流感病毒感染 24 小时内，T 细胞在肺部的积累量更高。与 T 细胞功能增强和向肺部迁移一致，艾奥洛斯缺陷型小鼠清除病毒的速度更快，相对于 WT 动物，发病率更低。从机制上讲，我们观察到艾奥洛斯抑制 T 细胞转录调节因子伊多美斯（Eomes）和白细胞介素-15 受体亚基 CD122（IL-15Rβ/IL-2Rβ），这两者是已知的 T 细胞生成的促成因素。总体而言，这些发现确立了艾奥洛斯是 T 细胞生成和功能的新型分子抑制因子。
