Language

English

Publication Date

10-28-2025

Journal

Cell Reports

DOI

10.1016/j.celrep.2025.116316

PMID

40974572

PMCID

PMC12509300

PubMedCentral® Posted Date

10-10-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

CD8+ T cell exhaustion limits immune responses during cancer and chronic infection. We identify CD7 as a tissue-specific regulator of terminally exhausted CD8+ T cells during chronic infection. CD7 expression progressively increases during exhaustion, reaching its highest levels on a subset of CD101+Tim3low terminally exhausted cells that arise in the liver. Transcriptomic analysis revealed that CD7-deficient terminally exhausted cells display altered expression of co-stimulatory, translational, and effector genes, correlating with markedly reduced persistence and increased apoptotic susceptibility. Importantly, CD7 is preferentially upregulated on PD-1+CD39+ tumor-infiltrating lymphocytes (TILs) in human head and neck squamous cell carcinoma (HNSCC), suggesting CD7 may play a conserved role in promoting exhausted T cell survival. These findings reveal a function for CD7 in sustaining terminally exhausted CD8+ T cells and demonstrate that CD7 signaling is a critical regulator of T cell persistence during chronic infection.

Keywords

CD8-Positive T-Lymphocytes, Humans, Animals, Persistent Infection, Mice, Inbred C57BL, Programmed Cell Death 1 Receptor, Mice, Apoptosis, Lymphocytes, Tumor-Infiltrating, Signal Transduction

Published Open-Access

yes

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