谷氨酰氨合酶代谢重编程是T细胞活化的标志。对抗原激活效应因子CD8+ T细胞进行同位素示踪分析表明，谷氨酸是合成多胺——腐胺、亚精胺和精胺的主要碳源。这些代谢物在活化诱导的T细胞增殖以及嘌呤中的产生起着重要作用，而嘌呤来源于亚精胺，与转运延长因子eIF5A形成共价键。本研究表明，谷氨酰氨合酶-多胺-嘌呤轴调控了CD69的表达，CD69是组织内驻留记忆T细胞（TRM）的重要调节因子。阻断这一回路可以增加TRM细胞在外周血液和骨髓中的体外和体内形成，骨髓是TRM细胞的明确位置。此外，阻断多胺-嘌呤轴可以增强人外周血液和肉瘤肿瘤浸润淋巴细胞中CD8+ T细胞的CD69表达以及IFN-γ和TNF-α的产生，同样对人CD8+CAR-T细胞也能起到同样的增加作用。综上所述，这些发现支持通过利用多胺-嘌呤回路来调节TRM细胞以获得治疗效果的观点。

Glutaminolysis is a hallmark of the activation and metabolic reprogramming of T cells. Isotopic tracer analyses of antigen-activated effector CD8+ T cells revealed that glutamine is the principal carbon source for the biosynthesis of polyamines putrescine, spermidine and spermine. These metabolites play critical roles in activation-induced T-cell proliferation, as well as for the production of hypusine, which is derived from spermidine and is covalently linked to the translation elongation factor eIF5A. Here, we demonstrated that the glutamine-polyamine-hypusine axis controls the expression of CD69, an important regulator of tissue resident memory T cells (TRM). Inhibition of this circuit augmented the development of TRM cells ex vivo and in vivo in the bone marrow, a well-established niche for TRM cells. Furthermore, blocking the polyamine-hypusine axis augmented CD69 expression and IFN-γ and TNF-α production in human CD8+ T cells from peripheral blood and sarcoma tumor infiltrating lymphocytes, as well as in human CD8+ CAR-T cells. Collectively, these findings support the notion that the polyamine-hypusine circuit can be exploited to modulate TRM cells for therapeutic benefit.