en
Scientific article
English

Expression of the DNA-binding factor TOX promotes the encephalitogenic potential of microbe-induced autoreactive CD8+ T cells

Published inImmunity, vol. 48, no. 5, p. 937-950.e8
Publication date2018
Abstract

Infections are thought to trigger CD8+ cytotoxic T lymphocyte (CTL) responses during autoimmunity. However, the transcriptional programs governing the tissue-destructive potential of CTLs remain poorly defined. In a model of central nervous system (CNS) inflammation, we found that infection with lymphocytic choriomeningitis virus (LCMV), but not Listeria monocytogenes (Lm), drove autoimmunity. The DNA-binding factor TOX was induced in CTLs during LCMV infection and was essential for their encephalitogenic properties, and its expression was inhibited by interleukin-12 during Lm infection. TOX repressed the activity of several transcription factors (including Id2, TCF-1, and Notch) that are known to drive CTL differentiation. TOX also reduced immune checkpoint sensitivity by restraining the expression of the inhibitory checkpoint receptor CD244 on the surface of CTLs, leading to increased CTL-mediated damage in the CNS. Our results identify TOX as a transcriptional regulator of tissue-destructive CTLs in autoimmunity, offering a potential mechanistic link to microbial triggers.

Citation (ISO format)
PAGE, Nicolas et al. Expression of the DNA-binding factor TOX promotes the encephalitogenic potential of microbe-induced autoreactive CD8+ T cells. In: Immunity, 2018, vol. 48, n° 5, p. 937–950.e8. doi: 10.1016/j.immuni.2018.04.005
Main files (1)
Article (Published version)
accessLevelRestricted
Updates (1)
Erratum
accessLevelRestricted
Identifiers
ISSN of the journal1074-7613
917views
19downloads

Technical informations

Creation06/07/2018 2:20:00 PM
First validation06/07/2018 2:20:00 PM
Update time03/15/2023 8:21:04 AM
Status update03/15/2023 8:21:03 AM
Last indexation01/17/2024 3:03:41 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack