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

Go to article

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.

Supported content

  1. Nature 571, 265–269 (2019). doi: 10.1038/s41586-019-1326-9
Institutions Share
TUM Chair Animal Physiology and Immunology, Germany 0.31
Department of Medicine II: Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, Uni Freiburg, Germany 0.10
The Mina and Everard Goodman Faculty of Life Sciences, BIU, Israel 0.10
TUM Institute of Molecular Immunology and Experimental Oncology (IMI), Germany 0.10
Department of Immunology, St. Jude, United States of America (USA) 0.08
The Peter Doherty Institute for Infection and Immunity (Doherty Institute), Australia 0.05
Department of Computational Biology, St. Jude, United States of America (USA) 0.05
TUM Institute of Pathology, Germany 0.05
Department of Pathology and Immunology, UNIGE, Switzerland 0.05
Swiss Institute of Bioinformatics (SIB), Switzerland 0.03
University of Lausanne (UNIL), Switzerland 0.03
Department of Oncology, UNIL, Switzerland 0.03
OSU Department of Microbial Infection and Immunity, United States of America (USA) 0.03