Very-low-carbohydrate diet triggers the endogenous production of ketone bodies as alternative energy substrates. There are as yet unproven assumptions that ketone bodies positively affect human immunity. We have investigated this topic in an in vitro model using primary human T cells and in an immuno-nutritional intervention study enrolling healthy volunteers. We show that ketone bodies profoundly impact human T-cell responses. CD4⁺, CD8⁺, and regulatory T-cell capacity were markedly enhanced, and T memory cell formation was augmented. RNAseq and functional metabolic analyses revealed a fundamental immunometabolic reprogramming in response to ketones favoring mitochondrial oxidative metabolism. This confers superior respiratory reserve, cellular energy supply, and reactive oxygen species signaling. Our data suggest a very-low-carbohydrate diet as a clinical tool to improve human T-cell immunity. Rethinking the value of nutrition and dietary interventions in modern medicine is required.

中文翻译：

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极低碳水化合物饮食通过免疫代谢重编程增强人类 T 细胞免疫力

极低碳水化合物饮食会引发酮体的内源性产生，作为替代能源底物。尚未证实酮体对人体免疫力有积极影响的假设。我们在使用原代人类 T 细胞的体外模型和招募健康志愿者的免疫营养干预研究中研究了这个主题。我们发现酮体深刻影响人类 T 细胞反应。CD4 ⁺、CD8 ⁺和调节性T细胞的能力显着增强，T记忆细胞的形成也增加。RNAseq 和功能代谢分析揭示了响应有利于线粒体氧化代谢的酮的基本免疫代谢重编程。这赋予了优越的呼吸储备、细胞能量供应和活性氧信号传导。我们的数据表明极低碳水化合物饮食可以作为改善人类 T 细胞免疫力的临床工具。需要重新思考现代医学中营养和饮食干预的价值。