TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection
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.
- Nature 571, 265–269 (2019). doi: 10.1038/s41586-019-1326-9