Nature Immunology, Published online: 13 April 2026; doi:10.1038/s41590-026-02494-7 Chronic antigen exposure drives TOX expression in CD8+ T cells and is associated with an exhausted hypofunctional T cell state. By contrast, data now show that the function of TOX in CD4+ T cells defines the TH1 lineage and supports the effector function of these cells.
Chronic antigen exposure drives TOX expression in CD8 + T cells and is associated with an exhausted hypofunctional T cell state. By contrast, data now show that the function of TOX in CD4 + T cells defines the T H 1 lineage and supports the effector function of these cells.
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Naizir, B. et al. Nat. Immunol. https://doi.org/10.1038/s41590-026-02453-2 (2026).
Gene Lay Institute of Immunology and Inflammation, Brigham and Women’s Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
Department of Neurology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
V.K.K. declares financial interests in: Bicara Therapeutics, Biocon Biologic, Catalio Capital, Compass, Elpiscience Biopharmaceutical Ltd, Equilium Inc, Larkspur Therapeutics, PerkinElmer/Revvity, Syngene Intl., Tizona Therapeutics, Trishula and Werewolf Therapeutics, Zumutor. V.K.K. is a member of scientific advisory boards for: Altru Bio, Biolegend/Revvity, Cell Signaling Technology, Elpiscience Biopharmaceutical Ltd, Larkspur, Noetik, Tr1X and Werewolf Therapeutics. Y.-C.K. declares no competing interests.
Kye, YC., Kuchroo, V.K. The dual role of TOX in regulating T H 1 and CD8 + T cell fate. Nat Immunol (2026). https://doi.org/10.1038/s41590-026-02494-7