@article{60f2a5bb0b024dc28febfe83c95700c9,
title = "The cell-surface 5′-nucleotidase CD73 defines a functional T memory cell subset that declines with age",
abstract = "Memory T cells exhibit considerable diversity that determines their ability to be protective. Here, we examine whether changes in T cell heterogeneity contribute to the age-associated failure of immune memory. By screening for age-dependent T cell-surface markers, we identify CD4 and CD8 memory T cell subsets that are unrelated to previously defined subsets of central and effector memory cells. Memory T cells expressing the ecto-5ʹ-nucleotidase CD73 constitute a functionally distinct subset of memory T cells that declines with age. They resemble long-lived, polyfunctional memory cells but are also poised to display effector functions and to develop into cells resembling tissue-resident memory T cells (TRMs). Upstream regulators of differential chromatin accessibility and transcriptomes include transcription factors that facilitate CD73 expression and regulate TRM differentiation. CD73 is not just a surrogate marker of these regulatory networks but is directly involved in T cell survival.",
keywords = "CD73, RUNX, T cell differentiation, adenosine, aging, heterogeneity, immunosenescence, memory T cell, tissue-residing memory T cells",
author = "Fengqin Fang and Wenqiang Cao and Weikang Zhu and Nora Lam and Lingjie Li and Sadhana Gaddam and Yong Wang and Chulwoo Kim and Simon Lambert and Huimin Zhang and Bin Hu and Farber, {Donna L.} and Weyand, {Cornelia M.} and Goronzy, {J{\"o}rg J.}",
note = "Funding Information: This work was supported by the National Institutes of Health ( R01 AR042527 , R01 HL117913 , R01 AI108906 , R01 HL142068 , and P01 HL129941 to C.M.W., P01 AI106697 to D.L.F., and R01 AI108891 , R01 AG045779 , U19 AI057266 , and R01 AI129191 to J.J.G.) and with resources and the use of facilities at the Palo Alto Veterans Administration Healthcare System . Network modeling was supported by National Natural Science Foundation of China (NSFC) grants (No. 11871463 , No. 12025107 , and No. 61621003 to Y.W.). N.L. was supported by NSF GRFP . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Flow cytometry and fluorescence activated cell sorting was performed in the Palo Alto Veteran Administration Flow Cytometry Core supported by the US Department of Veterans Affairs and the Palo Alto Veterans Institute for Research. Technical assistance was provided by Dr. Brandon Carter. Correlation analysis of transcriptomes between CD73 + and CD73 – cells versus T EM and T CM cells were done with help of Feng Zhang from Shanghai Jiaotong University School of Medicine (Shanghai, China). Funding Information: This work was supported by the National Institutes of Health (R01 AR042527, R01 HL117913, R01 AI108906, R01 HL142068, and P01 HL129941 to C.M.W. P01 AI106697 to D.L.F. and R01 AI108891, R01 AG045779, U19 AI057266, and R01 AI129191 to J.J.G.) and with resources and the use of facilities at the Palo Alto Veterans Administration Healthcare System. Network modeling was supported by National Natural Science Foundation of China (NSFC) grants (No. 11871463, No. 12025107, and No. 61621003 to Y.W.). N.L. was supported by NSF GRFP. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Flow cytometry and fluorescence activated cell sorting was performed in the Palo Alto Veteran Administration Flow Cytometry Core supported by the US Department of Veterans Affairs and the Palo Alto Veterans Institute for Research. Technical assistance was provided by Dr. Brandon Carter. Correlation analysis of transcriptomes between CD73+ and CD73? cells versus TEM and TCM cells were done with help of Feng Zhang from Shanghai Jiaotong University School of Medicine (Shanghai, China). F.F. W.C. D.L.F. C.M.W. and J.J.G. designed research and analyzed data. F.F. W.C. N. L. L.L. and C.K. performed the experimental work. W.Z. and Y.W. performed the network analysis. S.G. analyzed high-throughput data. S.L. H.Z. and B.H. recruited donors. F.F. Y.W. and J.J.G. wrote the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = nov,
day = "9",
doi = "10.1016/j.celrep.2021.109981",
language = "English",
volume = "37",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "6",
}