Although mucosal-associated invariant T (MAIT) cells provide rapid, innate-like responses, they are not pre-set, and memory-like responses have been described for MAIT cells following infections. The importance of metabolism for controlling these responses, however, is unknown. Here, following pulmonary immunization with a Salmonella vaccine strain, mouse MAIT cells expanded as separate CD127⁻Klrg1⁺ and CD127⁺Klrg1⁻ antigen-adapted populations that differed in terms of their transcriptome, function and localization in lung tissue. These populations remained altered from steady state for months as stable, separate MAIT cell lineages with enhanced effector programmes and divergent metabolism. CD127⁺ MAIT cells engaged in an energetic, mitochondrial metabolic programme, which was critical for their maintenance and IL-17A synthesis. This programme was supported by high fatty acid uptake and mitochondrial oxidation and relied on highly polarized mitochondria and autophagy. After vaccination, CD127⁺ MAIT cells protected mice against Streptococcus pneumoniae infection. In contrast, Klrg1⁺ MAIT cells had dormant but ready-to-respond mitochondria and depended instead on Hif1a-driven glycolysis to survive and produce IFN-γ. They responded antigen independently and participated in protection from influenza virus. These metabolic dependencies may enable tuning of memory-like MAIT cell responses for vaccination and immunotherapies.

尽管粘膜相关不变 T (MAIT) 细胞提供快速、先天性反应，但它们不是预先设定的，并且已经描述了 MAIT 细胞在感染后的记忆样反应。然而，新陈代谢对于控制这些反应的重要性尚不清楚。在这里，用沙门氏菌疫苗株进行肺部免疫后，小鼠 MAIT 细胞扩增为单独的 CD127 ^- Klrg1 ⁺和 CD127 ⁺ Klrg1 ^-抗原适应群体，其转录组、功能和在肺组织中的定位不同。这些群体在几个月内保持稳定状态的变化，成为稳定、独立的 MAIT 细胞谱系，具有增强的效应程序和不同的代谢。CD127 ⁺ MAIT 细胞参与充满活力的线粒体代谢程序，这对于它们的维持和 IL-17A 合成至关重要。该程序由高脂肪酸摄取和线粒体氧化支持，并依赖于高度极化的线粒体和自噬。接种疫苗后，CD127 ⁺ MAIT 细胞可保护小鼠免受肺炎链球菌感染。相比之下，Klrg1 ⁺ MAIT 细胞具有休眠但准备响应的线粒体，并且依赖 Hif1a 驱动的糖酵解来生存并产生 IFN-γ。它们独立地响应抗原并参与对流感病毒的保护。这些代谢依赖性可能能够调整类似记忆的 MAIT 细胞反应，以进行疫苗接种和免疫治疗。