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

Pereira, Branca I., De Maeyer, Roel P. H., Covre, Luciana P., Nehar-Belaid, Djamel, Lanna, Alessio, Ward, Sophie, Marches, Radu, Chambers, Emma S., Gomes, Daniel C. O., Riddell, Natalie E. , Maini, Mala K., Teixeira, Vitor H., Janes, Samuel M., Gilroy, Derek W., Larbi, Anis, Mabbott, Neil A., Ucar, Duygu, Kuchel, George A., Henson, Sian M., Strid, Jessica, Lee, Jun H., Banchereau, Jacques and Akbar, Arne N. (2020) Sestrins induce natural killer function in senescent-like CD8⁺ T cells Nature Immunology, 21 (6). pp. 684-694.

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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.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
Pereira, Branca I.
De Maeyer, Roel P. H.
Covre, Luciana P.
Nehar-Belaid, Djamel
Lanna, Alessio
Ward, Sophie
Marches, Radu
Chambers, Emma S.
Gomes, Daniel C. O.
Riddell, Natalie
Maini, Mala K.
Teixeira, Vitor H.
Janes, Samuel M.
Gilroy, Derek W.
Larbi, Anis
Mabbott, Neil A.
Ucar, Duygu
Kuchel, George A.
Henson, Sian M.
Strid, Jessica
Lee, Jun H.
Banchereau, Jacques
Akbar, Arne N.
Date : 30 March 2020
Funders : Biotechnology and Biological Sciences Research Council (BBSRC), Medical Research Council (MRC), Wellcome Trust, National Institutes of Health, National Institute for Health Research (NIHR)
DOI : 10.1038/s41590-020-0643-3
Copyright Disclaimer : © The Author(s), under exclusive licence to Springer Nature America, Inc. 2020
Depositing User : Clive Harris
Date Deposited : 27 May 2020 16:31
Last Modified : 01 Oct 2020 02:08

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