T cell activation is associated with increase in glycolysis and glutaminolysis. T cell immunoglobulin and mucin domain containing protein-3 (TIM-3), a T cell surface molecule, downregulates T cell activation and leads to insufficient immunity in cancer and chronic infection. TIM-3 regulates T cell activation possibly through alterations in metabolism; however, the relationship between TIM-3 expression and T cell metabolic changes has not been well studied. We investigated the association between TIM-3 expression and metabolic changes by analyzing glucose metabolism, glutamine metabolism, and mitochondrial function in TIM-3 overexpressing or knockout Jurkat T cell lines relative to their control cell lines. Glucose uptake and consumption, and lactate release were downregulated by TIM-3 expression but upregulated by TIM-3 knockout. Concomitantly, the expression of the glucose transporter, Glut1, but not Glut2, 3, or 4 was altered by TIM-3 expression. However, TIM-3 expression alone could not account for the change in glutamine consumption, glutamate release, and mitochondrial mass, ROS production or membrane potential in these cell lines. Our results show the association of TIM-3 expression with T cell glucose metabolism. These results are significant in chronic infections and cancers where it is necessary to control TIM-3 expressing T cells.

中文翻译：

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TIM-3 表达与 Jurkat T 细胞中葡萄糖代谢的关联。

T 细胞活化与糖酵解和谷氨酰胺分解的增加有关。T 细胞免疫球蛋白和含粘蛋白结构域的蛋白 3 (TIM-3)，一种 T 细胞表面分子，下调 T 细胞活化并导致癌症和慢性感染的免疫力不足。TIM-3 可能通过代谢改变来调节 T 细胞活化；然而，TIM-3 表达与 T 细胞代谢变化之间的关系尚未得到很好的研究。我们通过分析 TIM-3 过表达或敲除 Jurkat T 细胞系相对于对照细胞系的葡萄糖代谢、谷氨酰胺代谢和线粒体功能，研究了 TIM-3 表达与代谢变化之间的关联。葡萄糖摄取和消耗以及乳酸释放被 TIM-3 表达下调，但被 TIM-3 敲除上调。同时，TIM-3 表达改变了葡萄糖转运蛋白 Glut1 而非 Glut2、3 或 4 的表达。然而，单独的 TIM-3 表达不能解释这些细胞系中谷氨酰胺消耗、谷氨酸释放和线粒体质量、ROS 产生或膜电位的变化。我们的结果显示了 TIM-3 表达与 T 细胞葡萄糖代谢的关联。这些结果在需要控制表达 TIM-3 的 T 细胞的慢性感染和癌症中具有重要意义。我们的结果显示了 TIM-3 表达与 T 细胞葡萄糖代谢的关联。这些结果在需要控制表达 TIM-3 的 T 细胞的慢性感染和癌症中具有重要意义。我们的结果显示了 TIM-3 表达与 T 细胞葡萄糖代谢的关联。这些结果在需要控制表达 TIM-3 的 T 细胞的慢性感染和癌症中具有重要意义。