TY - JOUR
T1 - Deep profiling deconstructs features associated with memory CD8+ T cell tissue residence
AU - Scott, Milcah
AU - Steier, Zoë
AU - Pierson, Mark J.
AU - Stolley, J. Michael
AU - O’Flanagan, Stephen D.
AU - Soerens, Andrew G.
AU - Wijeyesinghe, Sathi P.
AU - Beura, Lalit K.
AU - Dileepan, Gayathri
AU - Burbach, Brandon J.
AU - Künzli, Marco
AU - Quarnstrom, Clare F.
AU - Smith, Olivia C. Ghirardelli
AU - Weyu, Eyob
AU - Hamilton, Sara E.
AU - Vezys, Vaiva
AU - Shalek, Alex K.
AU - masopust, david
N1 - Publisher Copyright:
© 2024
PY - 2025/1/14
Y1 - 2025/1/14
N2 - Tissue-resident memory CD8+ T (Trm) cells control infections and cancer and are defined by their lack of recirculation. Because migration is difficult to assess, residence is usually inferred by putative residence-defining phenotypic and gene signature proxies. We assessed the validity and universality of residence proxies by integrating mouse parabiosis, multi-organ sampling, intravascular staining, acute and chronic infection models, dirty mice, and single-cell multi-omics. We report that memory T cells integrate a constellation of inputs—location, stimulation history, antigen persistence, and environment—resulting in myriad differentiation states. Thus, current Trm-defining methodologies have implicit limitations, and a universal residence-specific signature may not exist. However, we define genes and phenotypes that more robustly correlate with tissue residence across the broad range of conditions that we tested. This study reveals broad adaptability of T cells to diverse stimulatory and environmental inputs and provides practical recommendations for evaluating Trm cells.
AB - Tissue-resident memory CD8+ T (Trm) cells control infections and cancer and are defined by their lack of recirculation. Because migration is difficult to assess, residence is usually inferred by putative residence-defining phenotypic and gene signature proxies. We assessed the validity and universality of residence proxies by integrating mouse parabiosis, multi-organ sampling, intravascular staining, acute and chronic infection models, dirty mice, and single-cell multi-omics. We report that memory T cells integrate a constellation of inputs—location, stimulation history, antigen persistence, and environment—resulting in myriad differentiation states. Thus, current Trm-defining methodologies have implicit limitations, and a universal residence-specific signature may not exist. However, we define genes and phenotypes that more robustly correlate with tissue residence across the broad range of conditions that we tested. This study reveals broad adaptability of T cells to diverse stimulatory and environmental inputs and provides practical recommendations for evaluating Trm cells.
UR - http://dx.doi.org/10.1016/j.immuni.2024.11.007
U2 - 10.1016/j.immuni.2024.11.007
DO - 10.1016/j.immuni.2024.11.007
M3 - Article
C2 - 39708817
SN - 1074-7613
VL - 58
SP - 162-181.e10
JO - Immunity
JF - Immunity
IS - 1
ER -