Abstract：
Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), is a major global health concern, particularly affecting those with weakened immune systems, including the elderly. CD4+ T cell response is crucial for immunity against M.tb, but chronic infections and aging can lead to T cell exhaustion and senescence, worsening TB disease. Mitochondrial dysfunction, prevalent in aging and chronic diseases, disrupts cellular metabolism, increases oxidative stress, and impairs T-cell functions. This study investigates the effect of mitochondrial transplantation (mito-transfer) on CD4+ T cell differentiation and function in aged mouse models and human CD4+ T cells from elderly individuals. Mito-transfer in naïve CD4+ T cells is found to promote protective effector and memory T cell generation during M.tb infection in mice. Additionally, it improves elderly human T cell function by increasing mitochondrial mass and altering cytokine production, thereby reducing markers of exhaustion and senescence. These findings suggest mito-transfer as a novel approach to enhance aged CD4+ T cell functionality, potentially benefiting immune responses in the elderly and chronic TB patients. This has broader implications for diseases where mitochondrial dysfunction contributes to T-cell exhaustion and senescence.
摘要：
结核病(TB),由结核分枝杆菌(M.tb),是全球主要的健康问题，特别是影响那些免疫系统较弱的人，包括老人。CD4+T细胞应答对M.tb免疫至关重要,但是慢性感染和衰老会导致T细胞衰竭和衰老，结核病恶化。线粒体功能障碍,在衰老和慢性疾病中普遍存在，破坏细胞新陈代谢，增加氧化应激，并损害T细胞功能。这项研究调查了线粒体移植（mito-transfer）对老年小鼠模型和老年人人CD4T细胞分化和功能的影响。发现初始CD4+T细胞中的米托转移在小鼠中的M.tb感染期间促进保护性效应和记忆T细胞生成。此外,它通过增加线粒体质量和改变细胞因子的产生来改善老年人T细胞功能，从而减少耗尽和衰老的标记。这些发现表明mito-transfer作为一种新的方法来增强老年CD4+T细胞的功能，可能有利于老年人和慢性结核病患者的免疫反应。这对线粒体功能障碍导致T细胞衰竭和衰老的疾病具有更广泛的意义。
