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

**Authors:** Jonas Bystrom, Melissa Pereira Da Costa, Amaia Carrascal-Miniño, Ahad Qureshi, George P. Keeling, Truc T. Pham, Kavitha Sunassee, Elizabeth C. Carroll, Conor Garrod-Ketchley, Johannes Schroth, Victoria S. K. Tsang, Rafael T. M. de Rosales, Samantha Y. A. Terry, Sian M. Henson

PMC · DOI: 10.1038/s41598-025-09237-y · 2025-07-03

## TL;DR

This study shows that CD8+ T cells from older individuals move more slowly in the body and may cause more tissue damage compared to those from younger individuals.

## Contribution

A method for radiolabelling and tracking cryopreserved CD8+ T cells in vivo using ⁸⁹Zr and PET imaging is established.

## Key findings

- CD8+ T cells from older individuals migrate more slowly and accumulate in tissues later than those from younger individuals.
- Aged T cells show decreased cortactin expression and increased cholesterol levels, which may impair their motility.
- The study provides a framework for assessing age-related functional deficits in T cells using PET imaging.

## 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.

The online version contains supplementary material available at 10.1038/s41598-025-09237-y.

## Linked entities

- **Proteins:** Cortactin (cortactin)
- **Chemicals:** zirconium-89 (PubChem CID 178156)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** CTTN (cortactin) [NCBI Gene 2017] {aka EMS1}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}
- **Diseases:** infections (MESH:D007239)
- **Chemicals:** cholesterol (MESH:D002784), 89Zr (MESH:C000615502)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12229634/full.md

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Source: https://tomesphere.com/paper/PMC12229634