Nature immunology · 2025
Tissue-resident exhausted and memory CD8+ T cells have distinct ontogeny, function and role in disease.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Park Simone L, Painter Mark M, Manne Sasikanth, Alcalde Victor, McLaughlin Maura, Sullivan Matthew A, Mathew Divij, Torres Leonel, Huang Yinghui J, Reeg David B, Douek Naomi R, Campos Trenton, Klapholz Max, Cardenas Maria A, Fang Victoria, Ngiow Shin Foong, Kc Wumesh, Goel Rishi R, Baxter Amy E, Wu Jennifer E, Tan Melody, Berry Corbett T, Ellebrecht Christoph T, Huang Alexander C, Papazian Emily, Liu Ying, Rajasekaran Karthik, Brody Robert M, Thaler Erica R, Basu Devraj, Diab Ahmed, Giles Josephine R, Wherry E John
Аннотация
The presence of CD8+ T cells coexpressing residency and exhaustion molecules in chronic diseases often correlate with clinical outcomes; however, the relationship between these cells and conventional tissue-resident memory (TRM) cells or exhausted CD8+ T (TEX) cells is unclear. Here we show that chronic antigen stimulation drives development of tissue-resident TEX (TR-TEX) cells that are distinct from TRM cells generated after antigen clearance. TR-TEX and TRM cells are regulated by different transcriptional networks with only TR-TEX cells being Tox-dependent for residency programming. While TEX cells (including TR-TEX) are unable to generate TRM cells after antigen withdrawal, TRM cells differentiate into TEX cells upon chronic antigen exposure. Cell-state-specific transcriptional signatures reveal a selective association of TR-TEX cells with patient responses to immune checkpoint blockade, and only TR-TEX but not TRM cells responded to PD-1 pathway inhibition in vivo. These data suggest that TR-TEX and TRM cells are developmentally divergent cell states that share a tissue-residency program but have distinct roles in disease control.