CD7 drives CD8 T cell exhaustion during chronic viral infection

Kayla Reisch; Amanda Scherer; Rebecca Bartell; Fernando Santana; Peng Shao; Noah S Butler; Ryan Zander

doi:10.1093/jimmun/vkag091

Back

CD7 drives CD8 T cell exhaustion during chronic viral infection

Journal article

Open access

Peer reviewed

CD7 drives CD8 T cell exhaustion during chronic viral infection

Kayla Reisch, Amanda Scherer, Rebecca Bartell, Fernando Santana, Peng Shao, Noah S Butler and Ryan Zander

The Journal of immunology (1950), Vol.215(6), vkag091

06/07/2026

DOI: 10.1093/jimmun/vkag091

PMID: 42258808

Files and links (1)

url

https://doi.org/10.1093/jimmun/vkag091View

Published (Version of record) Open Access

Abstract

Viral or tumor persistence is often associated with CD8 T cell "exhaustion," a differentiation process characterized by co-inhibitory receptor upregulation and loss of effector function. Recent data show that "exhausted" T cells are a heterogenous population that includes a progenitor subset that transitions through an intermediate state before bifurcating into either terminally exhausted cells or cytolytic effector cells crucial for viral or tumor control. However, the mechanisms underlying this bifurcation process remains unclear. In this study, we show that the Ig superfamily member CD7 is selectively upregulated on terminally exhausted T cells responding to chronic viral infection and cancer. Genetic deletion of CD7 in virus-specific CD8 T cells resulted in an expansion of effector T cells and reduced exhausted T cell formation, decreased inhibitory receptor expression, and augmented IFN-γ secretion following chronic lymphocytic choriomeningitis virus (LCMV) infection in mice. Deletion of CD7 in antigen-specific CD8 T cells conferred enhanced control over viral replication during chronic LCMV infection and suppressed tumor outgrowth in a preclinical lung cancer model. Conversely, retroviral overexpression of CD7 was sufficient to drive T cell exhaustion and upregulate expression of immune checkpoint inhibitory receptors and the transcription factor Tox. Mechanistically, our data indicate that CD7 may function to amplify TCR signaling strength and the induction of TCR-sensitive transcription factors such as Nur77 and Tox that program T cell exhaustion. These data highlight CD7 as a potential therapeutic target that can be manipulated to improve effector CD8 T cell-mediated control over chronic infection and/or malignancy.

Animals

CD8-Positive T-Lymphocytes - immunology

CD8-Positive T-Lymphocytes - metabolism

Chronic Disease

Lung Neoplasms - immunology

Lymphocytic Choriomeningitis - immunology

Lymphocytic choriomeningitis virus - immunology

Lymphocytic choriomeningitis virus - physiology

Mice

Mice, Inbred C57BL

Mice, Knockout

Persistent Infection - immunology

T-Cell Exhaustion

Details

Title: Subtitle: CD7 drives CD8 T cell exhaustion during chronic viral infection
Creators: Kayla Reisch - University of Iowa
Amanda Scherer - University of Iowa
Rebecca Bartell - University of Iowa
Fernando Santana - University of Iowa, Microbiology and Immunology
Peng Shao - University of Iowa
Noah S Butler - University of Iowa
Ryan Zander - University of Iowa
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.215(6), vkag091
DOI: 10.1093/jimmun/vkag091
PMID: 42258808
NLM abbreviation: J Immunol
ISSN: 1550-6606
eISSN: 1550-6606
Publisher: Oxford University Press
Grant note: AI125446 / National Institute of Health AI196779 / National Institute of Health T32AI007485 / Interdisciplinary Immunology T32 Predoctoral training grant from the National Institute of Allergy and Infectious Diseases AI196839 / National Institute of Health AI153537 / National Institute of Health AI167058 / National Institute of Health AI127481 / National Institute of Health
Language: English
Date published: 06/07/2026
Academic Unit: Molecular Physiology and Biophysics; Microbiology and Immunology
Record Identifier: 9985174500202771

Metrics

1 Record Views