TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection

Journal: Nature

Published: 2019-06-17

DOI: 10.1038/s41586-019-1326-9

Affiliations: 13

Authors: 20

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Research Highlight

Tired T cells? Blame TOX

© Photolibrary/Getty

© Photolibrary/Getty

During cancer and certain viral infections, disease-fighting immune cells progressively enter a dysfunctional, ‘exhausted’ state — and a newly discovered regulatory protein helps explain why.

A team co-led by researchers from the Technical University of Munich showed in mice and humans that chronic exposure to viruses elevated levels of a protein called TOX and led to the maintenance of T cells with a reduced ability to fight disease.

Eliminating the part of TOX needed for DNA binding helped keep T cells in an active state for longer, but the T cells ultimately became overstimulated and died off. TOX thus serves a dual role: promoting T cell exhaustion and maintaining large numbers of functional T cells.

Targeting TOX with drugs could help improve the durability of immunotherapies for cancer and infectious diseases — but, the authors caution, any modulation of TOX activity must be carefully fine-tuned to ensure the long-term survival of T cells.

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  1. Nature 571, 265–269 (2019). doi: 10.1038/s41586-019-1326-9
Institutions Share
Technical University of Munich (TUM), Germany 0.31
TUM University Hospital Klinikum rechts der Isar (MRI), Germany 0.15
St. Jude Children's Research Hospital (St. Jude), United States of America (USA) 0.13
University Medical Center Freiburg, Germany 0.10
Bar-Ilan University (BIU), Israel 0.10
The Peter Doherty Institute for Infection and Immunity (Doherty Institute), Australia 0.05
University of Geneva (UNIGE), Switzerland 0.05
Swiss Institute of Bioinformatics (SIB), Switzerland 0.03
University of Lausanne (UNIL), Switzerland 0.03
University Hospital of Lausanne (CHUV), UNIL, Switzerland 0.03
The Ohio State University (OSU), United States of America (USA) 0.03