Stem-like memory and precursors of exhausted T cells share a common progenitor defined by ID3 expression

Gago da Gra&#231;a, C; Sheikh, AA; Newman, DM; Wen, L; Li, S; Shen, J; Zhang, Y; Gabriel, SS; Chisanga, D; Seow, J; Poch, A; Rausch, L; Nguyen, MT; Singh, J; Su, CH; Cluse, LA; Tsui, C; Burn, TN; Park, SL; von Scheidt, B; Mackay, LK; Vasanthakumar, A; Bending, D; Shi, W; Cui, W; Schr&#246;der, J; Johnstone, RW; Kallies, A; Utzschneider, DT

Author(s): Gago da Graça, C; Sheikh, AA; Newman, DM; Wen, L; Li, S; Shen, J; Zhang, Y; Gabriel, SS; Chisanga, D; Seow, J; Poch, A; Rausch, L; Nguyen, MT; Singh, J; Su, CH; Cluse, LA; Tsui, C; Burn, TN; Park, SL; von Scheidt, B; Mackay, LK; Vasanthakumar, A; Bending, D; Shi, W; Cui, W; Schröder, J; Johnstone, RW; Kallies, A; Utzschneider, DT;
Details: Publication Year 2025-01-31,Volume 10,Issue #103,Page eadn1945
Journal Title: Science Immunology
Publication Type: Research article
Abstract: Stem-like T cells are attractive immunotherapeutic targets in patients with cancer given their ability to proliferate and differentiate into effector progeny. Thus, identifying T cells with enhanced stemness and understanding their developmental requirements are of broad clinical and therapeutic interest. Here, we demonstrate that during acute infection, the transcriptional regulator inhibitor of DNA binding 3 (ID3) identifies stem-like T cells that are uniquely adapted to generate precursors of exhausted T (Tpex) cells in response to chronic infection or cancer. Expression of ID3 itself enables Tpex cells to sustain T cell responses in chronic infection or cancer, whereas loss of ID3 results in impaired maintenance of CD8 T cell immunity. Furthermore, we demonstrate that interleukin-1 (IL-1) family members, including IL-36β and IL-18, promote the generation of ID3(+) T cells that mediate superior tumor control. Overall, we identify ID3 as a common denominator of stem-like T cells in both acute and chronic infections that is specifically required to sustain T cell responses to chronic stimulation.
Publisher: American Association for the Advancement of Science
Keywords: *Inhibitor of Differentiation Proteins/genetics/immunology; Animals; Mice; *Mice, Inbred C57BL; CD8-Positive T-Lymphocytes/immunology; Immunologic Memory/immunology; Mice, Knockout; Humans; Memory T Cells/immunology
Department(s): Laboratory Research
Publisher's Version: https://doi.org/10.1126/sciimmunol.adn1945
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-02-04 07:05:24

Last Modified: 2025-02-04 07:05:55