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

Branca I.  Pereira; Roel P. H.  De Maeyer; Luciana P.  Covre; Djamel  Nehar-Belaid; Alessio Lanna; Sophie Ward; Radu Marches; Emma S Chambers; Daniel C. O. Gomes; Natalie E.  Riddell; Mala K.  Maini; Vitor H.  Teixeira; Samuel M.  Janes; Derek W Gilroy; Anis Larbi; Neil Mabbott; Duyga Ucar; George A.  Kuchel; Sian M.  Henson; Jessica  Strid; Jun H.  Lee; Jacques Banchereau; Arne N Akbar

doi:10.1038/s41590-020-0643-3

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

Branca I. Pereira, Roel P. H. De Maeyer , Luciana P. Covre, Djamel Nehar-Belaid, Alessio Lanna, Sophie Ward , Radu Marches , Emma S Chambers, Daniel C. O. Gomes , Natalie E. Riddell , Mala K. Maini, Vitor H. Teixeira, Samuel M. Janes , Derek W Gilroy, Anis Larbi, Neil Mabbott, Duyga Ucar, George A. Kuchel, Sian M. Henson, Jessica StridJun H. Lee , Jacques Banchereau , Arne N Akbar

Research output: Contribution to journal › Article › peer-review

Abstract

Ageing is associated with re-modelling of the immune system to enable the maintenance of life-long immunity. In the CD8+ T cell compartment, ageing results in the expansion of highly differentiated cells that exhibit characteristics of cellular senescence. Here we found that CD27-CD28-CD8+ T lost the signalling activity of the T cell antigen receptor (TCR) and expressed a protein complex containing the agonistic 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 (Sesn2). The genetic inhibition of Sesn2 resulted in decreased expression of NKG2D and DAP12 and restored TCR signaling in senescent-like CD27-CD28-CD8+ T cells. Therefore, during ageing, sestrins induces the reprogramming of non-proliferative senescent-like CD27-CD28-CD8+ T cells to acquire a broad-spectrum,
innate-like killing activity.

Original language	English
Journal	Nature Immunology
DOIs	https://doi.org/10.1038/s41590-020-0643-3
Publication status	Published - 30 Mar 2020

Keywords

CD8-positive T cells
Cellular immunity
Immunosurveillance

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Pereira, B. I., De Maeyer , R. P. H., Covre, L. P., Nehar-Belaid, D., Lanna, A., Ward , S., Marches , R., Chambers, E. S., Gomes , D. C. O., Riddell , N. E., Maini, M. K., Teixeira, V. H., Janes , S. M., Gilroy, D. W., Larbi, A., Mabbott, N., Ucar, D., Kuchel, G. A., Henson, S. M., ... Akbar, A. N. (2020). Sestrins induce natural killer function in senescent-like CD8+ T cells. Nature Immunology. https://doi.org/10.1038/s41590-020-0643-3

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title = "Sestrins induce natural killer function in senescent-like CD8+ T cells",

abstract = "Ageing is associated with re-modelling of the immune system to enable the maintenance of life-long immunity. In the CD8+ T cell compartment, ageing results in the expansion of highly differentiated cells that exhibit characteristics of cellular senescence. Here we found that CD27-CD28-CD8+ T lost the signalling activity of the T cell antigen receptor (TCR) and expressed a protein complex containing the agonistic 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 (Sesn2). The genetic inhibition of Sesn2 resulted in decreased expression of NKG2D and DAP12 and restored TCR signaling in senescent-like CD27-CD28-CD8+ T cells. Therefore, during ageing, sestrins induces the reprogramming of non-proliferative senescent-like CD27-CD28-CD8+ T cells to acquire a broad-spectrum,innate-like killing activity.",

keywords = "CD8-positive T cells, Cellular immunity, Immunosurveillance",

author = "Pereira, {Branca I.} and {De Maeyer}, {Roel P. H.} and Covre, {Luciana P.} and Djamel Nehar-Belaid and Alessio Lanna and Sophie Ward and Radu Marches and Chambers, {Emma S} and Gomes, {Daniel C. O.} and Riddell, {Natalie E.} and Maini, {Mala K.} and Teixeira, {Vitor H.} and Janes, {Samuel M.} and Gilroy, {Derek W} and Anis Larbi and Neil Mabbott and Duyga Ucar and Kuchel, {George A.} and Henson, {Sian M.} and Jessica Strid and Lee, {Jun H.} and Jacques Banchereau and Akbar, {Arne N}",

year = "2020",

month = mar,

day = "30",

doi = "10.1038/s41590-020-0643-3",

language = "English",

journal = "Nature Immunology",

issn = "1529-2908",

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Pereira, BI, De Maeyer , RPH, Covre, LP, Nehar-Belaid, D, Lanna, A, Ward , S, Marches , R, Chambers, ES, Gomes , DCO, Riddell , NE, Maini, MK, Teixeira, VH, Janes , SM, Gilroy, DW, Larbi, A, Mabbott, N, Ucar, D, Kuchel, GA, Henson, SM, Strid, J, Lee , JH, Banchereau , J & Akbar, AN 2020, 'Sestrins induce natural killer function in senescent-like CD8+ T cells', Nature Immunology. https://doi.org/10.1038/s41590-020-0643-3

TY - JOUR

T1 - Sestrins induce natural killer function in senescent-like CD8+ T cells

AU - Pereira, Branca I.

AU - De Maeyer , Roel P. H.

AU - Covre, Luciana P.

AU - Nehar-Belaid, Djamel

AU - Lanna, Alessio

AU - Ward , Sophie

AU - Marches , Radu

AU - Chambers, Emma S

AU - Gomes , Daniel C. O.

AU - Riddell , Natalie E.

AU - Maini, Mala K.

AU - Teixeira, Vitor H.

AU - Janes , Samuel M.

AU - Gilroy, Derek W

AU - Larbi, Anis

AU - Mabbott, Neil

AU - Ucar, Duyga

AU - Kuchel, George A.

AU - Henson, Sian M.

AU - Strid, Jessica

AU - Lee , Jun H.

AU - Banchereau , Jacques

AU - Akbar, Arne N

PY - 2020/3/30

Y1 - 2020/3/30

N2 - Ageing is associated with re-modelling of the immune system to enable the maintenance of life-long immunity. In the CD8+ T cell compartment, ageing results in the expansion of highly differentiated cells that exhibit characteristics of cellular senescence. Here we found that CD27-CD28-CD8+ T lost the signalling activity of the T cell antigen receptor (TCR) and expressed a protein complex containing the agonistic 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 (Sesn2). The genetic inhibition of Sesn2 resulted in decreased expression of NKG2D and DAP12 and restored TCR signaling in senescent-like CD27-CD28-CD8+ T cells. Therefore, during ageing, sestrins induces the reprogramming of non-proliferative senescent-like CD27-CD28-CD8+ T cells to acquire a broad-spectrum,innate-like killing activity.

AB - Ageing is associated with re-modelling of the immune system to enable the maintenance of life-long immunity. In the CD8+ T cell compartment, ageing results in the expansion of highly differentiated cells that exhibit characteristics of cellular senescence. Here we found that CD27-CD28-CD8+ T lost the signalling activity of the T cell antigen receptor (TCR) and expressed a protein complex containing the agonistic 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 (Sesn2). The genetic inhibition of Sesn2 resulted in decreased expression of NKG2D and DAP12 and restored TCR signaling in senescent-like CD27-CD28-CD8+ T cells. Therefore, during ageing, sestrins induces the reprogramming of non-proliferative senescent-like CD27-CD28-CD8+ T cells to acquire a broad-spectrum,innate-like killing activity.

KW - CD8-positive T cells

KW - Cellular immunity

KW - Immunosurveillance

U2 - 10.1038/s41590-020-0643-3

DO - 10.1038/s41590-020-0643-3

M3 - Article

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

ER -

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

Abstract

Keywords

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