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Autoreactive T effector memory differentiation mirrors β cell function in type 1 diabetes

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Autoreactive T effector memory differentiation mirrors β cell function in type 1 diabetes. / Yeo, Lorraine; Woodwyk, Alyssa; Sood, Sanjana; Lorenc, Anna; Eichmann, Martin; Pujol-Autonell, Irma; Melchiotti, Rosella; Skowera, Ania; Fidanis, Efthymios; Dolton, Garry M.; Tungatt, Katie; Sewell, Andrew K.; Heck, Susanne; Saxena, Alka; Beam, Craig A.; Peakman, Mark.

In: Journal of Clinical Investigation, Vol. 128, No. 8, 01.08.2018, p. 3460-3474.

Research output: Contribution to journalArticle

Harvard

Yeo, L, Woodwyk, A, Sood, S, Lorenc, A, Eichmann, M, Pujol-Autonell, I, Melchiotti, R, Skowera, A, Fidanis, E, Dolton, GM, Tungatt, K, Sewell, AK, Heck, S, Saxena, A, Beam, CA & Peakman, M 2018, 'Autoreactive T effector memory differentiation mirrors β cell function in type 1 diabetes', Journal of Clinical Investigation, vol. 128, no. 8, pp. 3460-3474. https://doi.org/10.1172/JCI120555

APA

Yeo, L., Woodwyk, A., Sood, S., Lorenc, A., Eichmann, M., Pujol-Autonell, I., ... Peakman, M. (2018). Autoreactive T effector memory differentiation mirrors β cell function in type 1 diabetes. Journal of Clinical Investigation, 128(8), 3460-3474. https://doi.org/10.1172/JCI120555

Vancouver

Yeo L, Woodwyk A, Sood S, Lorenc A, Eichmann M, Pujol-Autonell I et al. Autoreactive T effector memory differentiation mirrors β cell function in type 1 diabetes. Journal of Clinical Investigation. 2018 Aug 1;128(8):3460-3474. https://doi.org/10.1172/JCI120555

Author

Yeo, Lorraine ; Woodwyk, Alyssa ; Sood, Sanjana ; Lorenc, Anna ; Eichmann, Martin ; Pujol-Autonell, Irma ; Melchiotti, Rosella ; Skowera, Ania ; Fidanis, Efthymios ; Dolton, Garry M. ; Tungatt, Katie ; Sewell, Andrew K. ; Heck, Susanne ; Saxena, Alka ; Beam, Craig A. ; Peakman, Mark. / Autoreactive T effector memory differentiation mirrors β cell function in type 1 diabetes. In: Journal of Clinical Investigation. 2018 ; Vol. 128, No. 8. pp. 3460-3474.

Bibtex Download

@article{c5e37c1d2b0541748896f57829832612,
title = "Autoreactive T effector memory differentiation mirrors β cell function in type 1 diabetes",
abstract = "In type 1 diabetes, cytotoxic CD8+ T cells with specificity for β cell autoantigens are found in the pancreatic islets, where they are implicated in the destruction of insulin-secreting β cells. In contrast, the disease relevance of β cell-reactive CD8+ T cells that are detectable in the circulation, and their relationship to β cell function, are not known. Here, we tracked multiple, circulating β cell-reactive CD8+ T cell subsets and measured β cell function longitudinally for 2 years, starting immediately after diagnosis of type 1 diabetes. We found that change in β cell-specific effector memory CD8+ T cells expressing CD57 was positively correlated with C-peptide change in subjects below 12 years of age. Autoreactive CD57+ effector memory CD8+ T cells bore the signature of enhanced effector function (higher expression of granzyme B, killer-specific protein of 37 kDa, and CD16, and reduced expression of CD28) compared with their CD57-counterparts, and network association modeling indicated that the dynamics of β cell-reactive CD57+ effector memory CD8+ T cell subsets were strongly linked. Thus, coordinated changes in circulating β cell-specific CD8+ T cells within the CD57+ effector memory subset calibrate to functional insulin reserve in type 1 diabetes, providing a tool for immune monitoring and a mechanism-based target for immunotherapy.",
author = "Lorraine Yeo and Alyssa Woodwyk and Sanjana Sood and Anna Lorenc and Martin Eichmann and Irma Pujol-Autonell and Rosella Melchiotti and Ania Skowera and Efthymios Fidanis and Dolton, {Garry M.} and Katie Tungatt and Sewell, {Andrew K.} and Susanne Heck and Alka Saxena and Beam, {Craig A.} and Mark Peakman",
year = "2018",
month = "8",
day = "1",
doi = "10.1172/JCI120555",
language = "English",
volume = "128",
pages = "3460--3474",
journal = "The Journal of clinical investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "8",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Autoreactive T effector memory differentiation mirrors β cell function in type 1 diabetes

AU - Yeo, Lorraine

AU - Woodwyk, Alyssa

AU - Sood, Sanjana

AU - Lorenc, Anna

AU - Eichmann, Martin

AU - Pujol-Autonell, Irma

AU - Melchiotti, Rosella

AU - Skowera, Ania

AU - Fidanis, Efthymios

AU - Dolton, Garry M.

AU - Tungatt, Katie

AU - Sewell, Andrew K.

AU - Heck, Susanne

AU - Saxena, Alka

AU - Beam, Craig A.

AU - Peakman, Mark

PY - 2018/8/1

Y1 - 2018/8/1

N2 - In type 1 diabetes, cytotoxic CD8+ T cells with specificity for β cell autoantigens are found in the pancreatic islets, where they are implicated in the destruction of insulin-secreting β cells. In contrast, the disease relevance of β cell-reactive CD8+ T cells that are detectable in the circulation, and their relationship to β cell function, are not known. Here, we tracked multiple, circulating β cell-reactive CD8+ T cell subsets and measured β cell function longitudinally for 2 years, starting immediately after diagnosis of type 1 diabetes. We found that change in β cell-specific effector memory CD8+ T cells expressing CD57 was positively correlated with C-peptide change in subjects below 12 years of age. Autoreactive CD57+ effector memory CD8+ T cells bore the signature of enhanced effector function (higher expression of granzyme B, killer-specific protein of 37 kDa, and CD16, and reduced expression of CD28) compared with their CD57-counterparts, and network association modeling indicated that the dynamics of β cell-reactive CD57+ effector memory CD8+ T cell subsets were strongly linked. Thus, coordinated changes in circulating β cell-specific CD8+ T cells within the CD57+ effector memory subset calibrate to functional insulin reserve in type 1 diabetes, providing a tool for immune monitoring and a mechanism-based target for immunotherapy.

AB - In type 1 diabetes, cytotoxic CD8+ T cells with specificity for β cell autoantigens are found in the pancreatic islets, where they are implicated in the destruction of insulin-secreting β cells. In contrast, the disease relevance of β cell-reactive CD8+ T cells that are detectable in the circulation, and their relationship to β cell function, are not known. Here, we tracked multiple, circulating β cell-reactive CD8+ T cell subsets and measured β cell function longitudinally for 2 years, starting immediately after diagnosis of type 1 diabetes. We found that change in β cell-specific effector memory CD8+ T cells expressing CD57 was positively correlated with C-peptide change in subjects below 12 years of age. Autoreactive CD57+ effector memory CD8+ T cells bore the signature of enhanced effector function (higher expression of granzyme B, killer-specific protein of 37 kDa, and CD16, and reduced expression of CD28) compared with their CD57-counterparts, and network association modeling indicated that the dynamics of β cell-reactive CD57+ effector memory CD8+ T cell subsets were strongly linked. Thus, coordinated changes in circulating β cell-specific CD8+ T cells within the CD57+ effector memory subset calibrate to functional insulin reserve in type 1 diabetes, providing a tool for immune monitoring and a mechanism-based target for immunotherapy.

UR - http://www.scopus.com/inward/record.url?scp=85051139305&partnerID=8YFLogxK

U2 - 10.1172/JCI120555

DO - 10.1172/JCI120555

M3 - Article

AN - SCOPUS:85051139305

VL - 128

SP - 3460

EP - 3474

JO - The Journal of clinical investigation

JF - The Journal of clinical investigation

SN - 0021-9738

IS - 8

ER -

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