SLAMF7 defines subsets of human effector CD8 T cells
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<sup>+</sup> 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.
Authors
- Ezequiel Ruíz-Mateos (ORCID: https://orcid.org/0000-0001-6747-7813)
- Josephine Lum (ORCID: https://orcid.org/0000-0003-1108-5989)
- Chin Hui Xian
- Anis Larbi (ORCID: https://orcid.org/0000-0001-8805-5433)
- Reena Rajasuriar (ORCID: https://orcid.org/0000-0003-3756-0629)
- Vipin Narang (ORCID: https://orcid.org/0000-0001-8669-9964)
- Aguan Wei (ORCID: https://orcid.org/0000-0003-2596-9240)
- Shu Wen Tan
- Hassen Kared (ORCID: https://orcid.org/0000-0002-8220-997X)
- Tze Pin Ng (ORCID: https://orcid.org/0000-0001-9585-855X)
- Adeeba Kamarulzaman
- Crystal Tan
Institutions
- Agency for Science, Technology and Research (SG)
- Oslo University Hospital (NO)
- The University of Melbourne (AU)
- National University of Singapore (SG)
- University of Oslo (NO)
- Singapore Immunology Network (SG)
- University of Malaya (MY)
- Peter Doherty Institute (AU)
- Instituto de Biomedicina de Sevilla (ES)
- Hospital Universitario Virgen del Rocío (ES)
- Universidad de Sevilla (ES)
Publication Details
- Journal
- Scientific Reports
- Published
- 2024-12-28
- DOI
- https://doi.org/10.1038/s41598-024-80971-5
- Citations
- 8
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 1.92
Funders
- International Society for Advancement of Cytometry
- Agency for Science, Technology and Research
- Consejo Superior de Investigaciones Científicas
- Instituto de Salud Carlos III
- Biomedical Research Council