Glycolysis facilitates the rapid recall response of CD8⁺ memory T (Tm) cells. However, it remains unclear whether Tm cells uptake exogenous glucose or mobilize endogenous sugar to fuel glycolysis. Here, we show that intracellular glycogen rather than extracellular glucose acts as the major carbon source for the early recall response. Following antigenic stimulation, Tm cells exhibit high glycogen phosphorylase (brain form, PYGB) activity, leading to glycogenolysis and release of glucose-6-phosphate (G6P). Elevated G6P mainly flows to glycolysis but is also partially channeled to the pentose phosphate pathway, which maintains the antioxidant capacity necessary for later recall stages. Mechanistically, TCR signaling directly induces phosphorylation of PYGB by LCK-ZAP70. Functionally, the glycogenolysis-fueled early recall response of CD8⁺ Tm cells accelerates the clearance of OVA-Listeria monocytogenes in an infected mouse model. Thus, we uncover a specific dependency on glycogen for the initial activation of memory T cells, which may have therapeutic implications for adaptive immunity.

糖酵解促进 CD8 ^{+的快速回忆反应}记忆 T (Tm) 细胞。然而，目前尚不清楚 Tm 细胞是摄取外源性葡萄糖还是动员内源性糖来促进糖酵解。在这里，我们表明细胞内糖原而不是细胞外葡萄糖是早期回忆反应的主要碳源。在抗原刺激后，Tm 细胞表现出高糖原磷酸化酶（脑型，PYGB）活性，导致糖原分解和葡萄糖-6-磷酸 (G6P) 的释放。升高的 G6P 主要流向糖酵解，但也部分流向戊糖磷酸途径，该途径维持后期回忆阶段所需的抗氧化能力。从机制上讲，TCR 信号通过 LCK-ZAP70 直接诱导 PYGB 的磷酸化。^{在功能上，CD8 +}的糖原分解促进了早期回忆反应Tm 细胞加速了受感染小鼠模型中 OVA-李斯特菌的清除。因此，我们揭示了记忆 T 细胞的初始激活对糖原的特定依赖性，这可能对适应性免疫具有治疗意义。