Impact of age on the homing potential of 89Zr-radiolabelled CD8 + T cells

Abstract

Abstract 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.