Sustained AhR activity programs memory fate of early effector CD8+ T cells

• 成果类型: Article
• 署名作者: Zhang, Huafeng; Yang, Zhuoshun; Yuan, Wu; Liu, Jincheng; Luo, Xiao; Zhang, Qian; Li, Yonggang; Chen, Jie; Zhou, Yabo; Lv, Jiadi; Zhou, Nannan; Ma, Jingwei; Tang, Ke; Huang, Bo
• 署名单位: Huazhong University of Science & Technology; Huazhong University of Science & Technology; Hubei University of Medicine; Huazhong University of Science & Technology; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; Huazhong University of Science & Technology
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9349
• DOI: 10.1073/pnas.2317658121
• 发表日期: 2024-03-12
• 关键词: aryl-hydrocarbon receptor; differentiation; expression; expansion; maintenance; activation; migration; division; subsets; PATHWAY

摘要

Identification of mechanisms that program early effector T cells to either terminal effector T (T-eff) or memory T (T-m) cells has important implications for protective immunity against infections and cancers. Here, we show that the cytosolic transcription factor aryl hydrocarbon receptor (AhR) is used by early T-eff cells to program memory fate. Upon antigen engagement, AhR is rapidly up-regulated via reactive oxygen species signaling in early CD8(+) T-eff cells, which does not affect the effector response, but is required for memory formation. Mechanistically, activated CD8(+) T cells up-regulate HIF-1 alpha to compete with AhR for HIF-1 beta, leading to the loss of AhR activity in HIF-1 alpha(high) short-lived effector cells, but sustained in HIF-1 alpha(low) memory precursor effector cells (MPECs) with the help of autocrine IL-2. AhR then licenses CD8(+) MPECs in a quiescent state for memory formation. These findings partially resolve the long-standing issue of how T-eff cells are regulated to differentiate into memory cells.