Bystrom Jonas, Da Costa Melissa Pereira, Carrascal-Miniño Amaia, Qureshi Ahad, Keeling George P, Pham Truc T, Sunassee Kavitha, Carroll Elizabeth C, Garrod-Ketchley Conor, Schroth Johannes, Tsang Victoria S K, de Rosales Rafael T M, Terry Samantha Y A, Henson Sian M
Centre for Translational Medicine and Therapeutics, William Harvey Research Institute, Queen Mary University of London, London, EC1M 6BQ, UK.
School of Biomedical Engineering & Imaging Sciences, King's College London, St Thomas' Hospital, London, SE1 7EH, UK.
Sci Rep. 2025 Jul 3;15(1):23801. doi: 10.1038/s41598-025-09237-y.
The ability of CD8 + T cells to protect against infections and malignant transformations declines with age. Emerging technologies, such as total body positron emission tomography (PET) and radiotracers with long half-lives, offer new approaches to assess long-term cellular functional deficits in vivo. In this study, we radiolabelled human CD8 + T cells from both young and old individuals with zirconium-89 (⁸⁹Zr) and evaluated their distribution in vivo. ⁸⁹Zr-labelled CD8 + T cells were injected intravenously into NOD scid gamma mice, and their whole-body migration was tracked using PET imaging. Longitudinal PET imaging revealed that CD8 + T cells from older individuals accumulated in tissues at a slower rate compared to those from younger individuals and may have caused greater tissue damage. This impaired migration was associated with decreased cortactin expression and increased cholesterol levels in aged T cells, both of which have the potential to hinder cellular motility. This study established a method for labelling and tracking cryopreserved CD8 + T cells, though further research is needed to understand the differences in migratory behaviour between cells from young and older individuals.
CD8 + T细胞抵御感染和恶性转化的能力会随着年龄增长而下降。新兴技术,如全身正电子发射断层扫描(PET)和具有长半衰期的放射性示踪剂,为在体内评估长期细胞功能缺陷提供了新方法。在本研究中,我们用锆 - 89(⁸⁹Zr)对年轻和老年个体的人类CD8 + T细胞进行放射性标记,并评估它们在体内的分布。将⁸⁹Zr标记的CD8 + T细胞静脉注射到NOD scid gamma小鼠体内,使用PET成像追踪它们在全身的迁移情况。纵向PET成像显示,与年轻个体的CD8 + T细胞相比,老年个体的CD8 + T细胞在组织中的积累速度较慢,并且可能造成更大的组织损伤。这种迁移受损与老年T细胞中皮层肌动蛋白表达降低和胆固醇水平升高有关,这两者都有可能阻碍细胞运动。本研究建立了一种标记和追踪冷冻保存的CD8 + T细胞的方法,不过还需要进一步研究以了解年轻和老年个体细胞迁移行为的差异。