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Sestrins induce natural killer function in senescent-like CD8+ T cells

Gilroy, D; Pereira, B; De Maeyer, R; covre, L; Nehar-Belaid, D; Lanna, A; Ward, S; ... Akbar, A; + view all (2020) Sestrins induce natural killer function in senescent-like CD8+ T cells. Nature Immunology , 21 pp. 684-694. 10.1038/s41590-020-0643-3. Green open access

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Abstract

Aging is associated with remodeling of the immune system to enable the maintenance of life-long immunity. In the CD8+ T cell compartment, aging results in the expansion of highly differentiated cells that exhibit characteristics of cellular senescence. Here we found that CD27−CD28−CD8+ T cells lost the signaling activity of the T cell antigen receptor (TCR) and expressed a protein complex containing the agonistic natural killer (NK) receptor NKG2D and the NK adaptor molecule DAP12, which promoted cytotoxicity against cells that expressed NKG2D ligands. Immunoprecipitation and imaging cytometry indicated that the NKG2D–DAP12 complex was associated with sestrin 2. The genetic inhibition of sestrin 2 resulted in decreased expression of NKG2D and DAP12 and restored TCR signaling in senescent-like CD27−CD28−CD8+ T cells. Therefore, during aging, sestrins induce the reprogramming of non-proliferative senescent-like CD27−CD28−CD8+ T cells to acquire a broad-spectrum, innate-like killing activity.

Type: Article
Title: Sestrins induce natural killer function in senescent-like CD8+ T cells
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41590-020-0643-3
Publisher version: https://doi.org/10.1038/s41590-020-0643-3
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: CD8-positive T cells, Cellular immunity, Immunosurveillance
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Department of Education
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10091200
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