Sustained AhR activity programs memory fate of early effector CD8 <sup>+</sup> T cells
Huafeng Zhang, Zhuoshun Yang, Yuan Wu, Jincheng Liu, Xiao Luo, Qian Zhang, Yonggang Li, Jie Chen, Yabo Zhou, Jiadi Lv, Nannan Zhou, Jingwei Ma, Ke Tang, Bo Huang
Abstract
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-1α to compete with AhR for HIF-1β, leading to the loss of AhR activity in HIF-1α high short-lived effector cells, but sustained in HIF-1α 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.