Islet-reactive CD8(+) T cell frequencies in the pancreas, but not in blood, distinguish type 1 diabetic patients from healthy donors

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Islet-reactive CD8(+) T cell frequencies in the pancreas, but not in blood, distinguish type 1 diabetic patients from healthy donors. / Culina, Slobodan; Lalanne, Ana Ines; Afonso, Georgia; Cerosaletti, Karen; Pinto, Sheena; Sebastiani, Guido; Kuranda, Klaudia; Nigi, Laura; Eugster, Anne; Osterbye, Thomas; Maugein, Alicia; McLaren, James E.; Ladell, Kristin; Larger, Etienne; Beressi, Jean-Paul; Lissina, Anna; Appay, Victor; Davidson, Howard W.; Buus, Soren; Price, David A.; Kuhn, Matthias; Bonifacio, Ezio; Battaglia, Manuela; Caillat-Zucman, Sophie; Dotta, Francesco; Scharfmann, Raphael; Kyewski, Bruno; Mallone, Roberto.

In: Science immunology, Vol. 3, No. 20, eaao4013, 2018.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Culina, S, Lalanne, AI, Afonso, G, Cerosaletti, K, Pinto, S, Sebastiani, G, Kuranda, K, Nigi, L, Eugster, A, Osterbye, T, Maugein, A, McLaren, JE, Ladell, K, Larger, E, Beressi, J-P, Lissina, A, Appay, V, Davidson, HW, Buus, S, Price, DA, Kuhn, M, Bonifacio, E, Battaglia, M, Caillat-Zucman, S, Dotta, F, Scharfmann, R, Kyewski, B & Mallone, R 2018, 'Islet-reactive CD8(+) T cell frequencies in the pancreas, but not in blood, distinguish type 1 diabetic patients from healthy donors', Science immunology, vol. 3, no. 20, eaao4013. https://doi.org/10.1126/sciimmunol.aao4013

APA

Culina, S., Lalanne, A. I., Afonso, G., Cerosaletti, K., Pinto, S., Sebastiani, G., Kuranda, K., Nigi, L., Eugster, A., Osterbye, T., Maugein, A., McLaren, J. E., Ladell, K., Larger, E., Beressi, J-P., Lissina, A., Appay, V., Davidson, H. W., Buus, S., ... Mallone, R. (2018). Islet-reactive CD8(+) T cell frequencies in the pancreas, but not in blood, distinguish type 1 diabetic patients from healthy donors. Science immunology, 3(20), [eaao4013]. https://doi.org/10.1126/sciimmunol.aao4013

Vancouver

Culina S, Lalanne AI, Afonso G, Cerosaletti K, Pinto S, Sebastiani G et al. Islet-reactive CD8(+) T cell frequencies in the pancreas, but not in blood, distinguish type 1 diabetic patients from healthy donors. Science immunology. 2018;3(20). eaao4013. https://doi.org/10.1126/sciimmunol.aao4013

Author

Culina, Slobodan ; Lalanne, Ana Ines ; Afonso, Georgia ; Cerosaletti, Karen ; Pinto, Sheena ; Sebastiani, Guido ; Kuranda, Klaudia ; Nigi, Laura ; Eugster, Anne ; Osterbye, Thomas ; Maugein, Alicia ; McLaren, James E. ; Ladell, Kristin ; Larger, Etienne ; Beressi, Jean-Paul ; Lissina, Anna ; Appay, Victor ; Davidson, Howard W. ; Buus, Soren ; Price, David A. ; Kuhn, Matthias ; Bonifacio, Ezio ; Battaglia, Manuela ; Caillat-Zucman, Sophie ; Dotta, Francesco ; Scharfmann, Raphael ; Kyewski, Bruno ; Mallone, Roberto. / Islet-reactive CD8(+) T cell frequencies in the pancreas, but not in blood, distinguish type 1 diabetic patients from healthy donors. In: Science immunology. 2018 ; Vol. 3, No. 20.

Bibtex

@article{329521f528134f63a31006984ee4cf6a,
title = "Islet-reactive CD8(+) T cell frequencies in the pancreas, but not in blood, distinguish type 1 diabetic patients from healthy donors",
abstract = "The human leukocyte antigen–A2 (HLA-A2)–restricted zinc transporter 8186–194 (ZnT8186–194) and other islet epitopes elicit interferon-γ secretion by CD8+ T cells preferentially in type 1 diabetes (T1D) patients compared with controls. We show that clonal ZnT8186–194-reactive CD8+ T cells express private T cell receptors and display equivalent functional properties in T1D and healthy individuals. Ex vivo analyses further revealed that CD8+ T cells reactive to ZnT8186–194 and other islet epitopes circulate at similar frequencies and exhibit a predominantly na{\"i}ve phenotype in age-matched T1D and healthy donors. Higher frequencies of ZnT8186–194-reactive CD8+ T cells with a more antigen-experienced phenotype were detected in children versus adults, irrespective of disease status. Moreover, some ZnT8186–194-reactive CD8+ T cell clonotypes were found to cross-recognize a Bacteroides stercoris mimotope. Whereas ZnT8 was poorly expressed in thymic medullary epithelial cells, variable thymic expression levels of islet antigens did not modulate the peripheral frequency of their cognate CD8+ T cells. In contrast, ZnT8186–194-reactive cells were enriched in the pancreata of T1D patients versus nondiabetic and type 2 diabetic individuals. Thus, islet-reactive CD8+ T cells circulate in most individuals but home to the pancreas preferentially in T1D patients. We conclude that the activation of this common islet-reactive T cell repertoire and progression to T1D likely require defective peripheral immunoregulation and/or a proinflammatory islet microenvironment.",
author = "Slobodan Culina and Lalanne, {Ana Ines} and Georgia Afonso and Karen Cerosaletti and Sheena Pinto and Guido Sebastiani and Klaudia Kuranda and Laura Nigi and Anne Eugster and Thomas Osterbye and Alicia Maugein and McLaren, {James E.} and Kristin Ladell and Etienne Larger and Jean-Paul Beressi and Anna Lissina and Victor Appay and Davidson, {Howard W.} and Soren Buus and Price, {David A.} and Matthias Kuhn and Ezio Bonifacio and Manuela Battaglia and Sophie Caillat-Zucman and Francesco Dotta and Raphael Scharfmann and Bruno Kyewski and Roberto Mallone",
year = "2018",
doi = "10.1126/sciimmunol.aao4013",
language = "English",
volume = "3",
journal = "Advances in Immunology",
issn = "0065-2776",
publisher = "American Association for the Advancement of Science",
number = "20",

}

RIS

TY - JOUR

T1 - Islet-reactive CD8(+) T cell frequencies in the pancreas, but not in blood, distinguish type 1 diabetic patients from healthy donors

AU - Culina, Slobodan

AU - Lalanne, Ana Ines

AU - Afonso, Georgia

AU - Cerosaletti, Karen

AU - Pinto, Sheena

AU - Sebastiani, Guido

AU - Kuranda, Klaudia

AU - Nigi, Laura

AU - Eugster, Anne

AU - Osterbye, Thomas

AU - Maugein, Alicia

AU - McLaren, James E.

AU - Ladell, Kristin

AU - Larger, Etienne

AU - Beressi, Jean-Paul

AU - Lissina, Anna

AU - Appay, Victor

AU - Davidson, Howard W.

AU - Buus, Soren

AU - Price, David A.

AU - Kuhn, Matthias

AU - Bonifacio, Ezio

AU - Battaglia, Manuela

AU - Caillat-Zucman, Sophie

AU - Dotta, Francesco

AU - Scharfmann, Raphael

AU - Kyewski, Bruno

AU - Mallone, Roberto

PY - 2018

Y1 - 2018

N2 - The human leukocyte antigen–A2 (HLA-A2)–restricted zinc transporter 8186–194 (ZnT8186–194) and other islet epitopes elicit interferon-γ secretion by CD8+ T cells preferentially in type 1 diabetes (T1D) patients compared with controls. We show that clonal ZnT8186–194-reactive CD8+ T cells express private T cell receptors and display equivalent functional properties in T1D and healthy individuals. Ex vivo analyses further revealed that CD8+ T cells reactive to ZnT8186–194 and other islet epitopes circulate at similar frequencies and exhibit a predominantly naïve phenotype in age-matched T1D and healthy donors. Higher frequencies of ZnT8186–194-reactive CD8+ T cells with a more antigen-experienced phenotype were detected in children versus adults, irrespective of disease status. Moreover, some ZnT8186–194-reactive CD8+ T cell clonotypes were found to cross-recognize a Bacteroides stercoris mimotope. Whereas ZnT8 was poorly expressed in thymic medullary epithelial cells, variable thymic expression levels of islet antigens did not modulate the peripheral frequency of their cognate CD8+ T cells. In contrast, ZnT8186–194-reactive cells were enriched in the pancreata of T1D patients versus nondiabetic and type 2 diabetic individuals. Thus, islet-reactive CD8+ T cells circulate in most individuals but home to the pancreas preferentially in T1D patients. We conclude that the activation of this common islet-reactive T cell repertoire and progression to T1D likely require defective peripheral immunoregulation and/or a proinflammatory islet microenvironment.

AB - The human leukocyte antigen–A2 (HLA-A2)–restricted zinc transporter 8186–194 (ZnT8186–194) and other islet epitopes elicit interferon-γ secretion by CD8+ T cells preferentially in type 1 diabetes (T1D) patients compared with controls. We show that clonal ZnT8186–194-reactive CD8+ T cells express private T cell receptors and display equivalent functional properties in T1D and healthy individuals. Ex vivo analyses further revealed that CD8+ T cells reactive to ZnT8186–194 and other islet epitopes circulate at similar frequencies and exhibit a predominantly naïve phenotype in age-matched T1D and healthy donors. Higher frequencies of ZnT8186–194-reactive CD8+ T cells with a more antigen-experienced phenotype were detected in children versus adults, irrespective of disease status. Moreover, some ZnT8186–194-reactive CD8+ T cell clonotypes were found to cross-recognize a Bacteroides stercoris mimotope. Whereas ZnT8 was poorly expressed in thymic medullary epithelial cells, variable thymic expression levels of islet antigens did not modulate the peripheral frequency of their cognate CD8+ T cells. In contrast, ZnT8186–194-reactive cells were enriched in the pancreata of T1D patients versus nondiabetic and type 2 diabetic individuals. Thus, islet-reactive CD8+ T cells circulate in most individuals but home to the pancreas preferentially in T1D patients. We conclude that the activation of this common islet-reactive T cell repertoire and progression to T1D likely require defective peripheral immunoregulation and/or a proinflammatory islet microenvironment.

U2 - 10.1126/sciimmunol.aao4013

DO - 10.1126/sciimmunol.aao4013

M3 - Journal article

C2 - 29429978

VL - 3

JO - Advances in Immunology

JF - Advances in Immunology

SN - 0065-2776

IS - 20

M1 - eaao4013

ER -

ID: 210065725