SLAMF7 defines subsets of human effector CD8 T cells

SLAMF7 defines subsets of human effector CD8 T cells

Scientific Reports

10.1038/s41598-024-80971-5

https://doi.org/10.1038/s41598-024-80971-5

Hassen Kared, Crystal Tan, Vipin Narang, Shu Wen Tan, Hui Xian Chin, Alicia Seok Wei Tay, Josephine Lum, Ezequiel Ruiz-Mateos, Reena Rajasuriar, Adeeba Kamarulzaman, Tze Pin Ng, Anis Larbi

viral infections, Cellular senescence, aging

28 December 2024

Kared, H., Tan, C., Narang, V., Tan, S. W., Xian, C. H., Wei, A. T. S., Lum, J., Ruiz-Mateos, E., Rajasuriar, R., Kamarulzaman, A., Ng, T. P., & Larbi, A. (2024). SLAMF7 defines subsets of human effector CD8 T cells. Scientific Reports, 14(1). https://doi.org/10.1038/s41598-024-80971-5

Long-term control of viral replication relies on the efficient differentiation of memory T cells into effector T cells during secondary immune responses. Recent findings have identified T cell precursors for both memory and exhausted T cells, suggesting the existence of progenitor-like effector T cells. These cells can persist without antigenic challenge but expand and acquire effector functions upon recall immune responses. In this study, we demonstrate that the combination of SLAMF7 with either CD27 or TCF-1 effectively identifies progenitor-like effector CD8 T cells, while SLAMF7 with GPR56 or TOX defines effector CD8 T cells. These markers allow for the clear segregation of these distinct cell subsets. SLAMF7+ CD8T cells are dynamically modulated during viral infections, including HIV, HCV, CMV, and SARS-CoV-2, as well as during aging. We further characterize the SLAMF7 signature at both phenotypic and transcriptional levels. Notably, during aging, the SLAMF7 pathway becomes dysregulated, resulting in persistent phosphorylation of STAT1. Additionally, SLAMF7 ligation in the presence of IL-15 induces TCF-1 expression, which promotes the homeostatic proliferation of progenitor-like effector CD8 T cells.

Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

This research / project is supported by the Agency for Science, Technology and Research (A*STAR), Biomedical Research Council (BMRC) - Industry Alignment Fund
Grant Reference no. : 311006

This research / project is supported by the Agency for Science, Technology and Research (A*STAR), Biomedical Research Council (BMRC) - Transition Funds
Grant Reference no. : H16/99/b0/011

This research / project is supported by the Agency for Science, Technology and Research (A*STAR), Biomedical Research Council (BMRC) - Industry Alignment Fund - Pre-Positioning
Grant Reference no. : H1901a0024

This research / project is supported by the National Research Foundation - Shared Infrastructure Support Grant
Grant Reference no. : NRF2017_SISFP09

This research is supported by core funding from: Singapore Immunology Network (SIgN)
Grant Reference no. : 10-036

https://oar.a-star.edu.sg/communities-collections/articles/21466

2045-2322

Singapore Immunology Network

https://www.nature.com/articles/s41598-024-80971-5.pdf