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Citations to this article

Autoreactive T cell responses show proinflammatory polarization in diabetes but a regulatory phenotype in health
Sefina Arif, … , Bart O. Roep, Mark Peakman
Sefina Arif, … , Bart O. Roep, Mark Peakman
Published February 1, 2004
Citation Information: J Clin Invest. 2004;113(3):451-463. https://doi.org/10.1172/JCI19585.
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Article Immunology

Autoreactive T cell responses show proinflammatory polarization in diabetes but a regulatory phenotype in health

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Abstract

According to the quality of response they mediate, autoreactive T cells recognizing islet β cell peptides could represent both disease effectors in the development of type 1 diabetes (T1DM) and directors of tolerance in nondiabetic individuals or those undergoing preventative immunotherapy. A combination of the rarity of these cells, inadequate technology, and poorly defined epitopes, however, has hampered examination of this paradigm. We have identified a panel of naturally processed islet epitopes by direct elution from APCs bearing HLA-DR4. Employing these epitopes in a sensitive, novel cytokine enzyme-linked immunosorbent spot assay, we show that the quality of autoreactive T cells in patients with T1DM exhibits extreme polarization toward a proinflammatory Th1 phenotype. Furthermore, we demonstrate that rather than being unresponsive, the majority of nondiabetic, HLA-matched control subjects also manifest a response against islet peptides, but one that shows extreme T regulatory cell (Treg, IL-10–secreting) bias. We conclude that development of T1DM depends on the balance of autoreactive Th1 and Treg cells, which may be open to favorable manipulation by immune intervention.

Authors

Sefina Arif, Timothy I. Tree, Thomas P. Astill, Jennifer M. Tremble, Amanda J. Bishop, Colin M. Dayan, Bart O. Roep, Mark Peakman

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 Total
Citations: 3 8 10 11 21 10 13 11 19 5 15 11 9 6 13 14 9 18 7 7 5 5 230
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2017 (19)

Title and authors Publication Year
Autoreactive T-cells in Type 1 Diabetes
Alberto Pugliese
Journal of Clinical Investigation 2017
miRNAs: novel regulators of autoimmunity-mediated pancreatic β-cell destruction in type 1 diabetes
Y Zheng, Z Wang, Z Zhou
Cellular and Molecular Immunology 2017
Type 1 Diabetes: A Chronic Anti-Self-Inflammatory Response
M Clark, CJ Kroger, RM Tisch
Frontiers in immunology 2017
Regulatory T cell dysfunction in type 1 diabetes: what’s broken and how can we fix it?
CM Hull, M Peakman, TI Tree
Diabetologia 2017
Harnessing the power of regulatory T-cells to control autoimmune diabetes: overview and perspective
H Yu, R Paiva, RA Flavell
Immunology 2017
T cell receptor β-chains display abnormal shortening and repertoire sharing in type 1 diabetes
I Gomez-Tourino, Y Kamra, R Baptista, A Lorenc, M Peakman
Nature Communications 2017
Deciphering the Pathogenesis of Human Type 1 Diabetes (T1D) by Interrogating T Cells from the “Scene of the Crime”
SC Kent, SI Mannering, AW Michels, JA Babon
Current Diabetes Reports 2017
Single-Cell RNA Sequencing Reveals Expanded Clones of Islet Antigen-Reactive CD4 + T Cells in Peripheral Blood of Subjects with Type 1 Diabetes
K Cerosaletti, F Barahmand-pour-Whitman, J Yang, HA DeBerg, MJ Dufort, SA Murray, E Israelsson, C Speake, VH Gersuk, JA Eddy, H Reijonen, CJ Greenbaum, WW Kwok, E Wambre, M Prlic, R Gottardo, GT Nepom, PS Linsley
Journal of immunology (Baltimore, Md. : 1950) 2017
APC‐targeted proinsulin expression inactivates insulin‐specific memory CD8 + T cells in NOD mice
PL Reeves, R Rudraraju, X Liu, FS Wong, EE HamiltonWilliams, RJ Steptoe
Immunology and Cell Biology 2017
Increased inflammation is associated with islet autoimmunity and type 1 diabetes in the Diabetes Autoimmunity Study in the Young (DAISY)
K Waugh, J Snell-Bergeon, A Michels, F Dong, AK Steck, BI Frohnert, JM Norris, M Rewers, IR Cohen
PloS one 2017
The elusive role of B lymphocytes and islet autoantibodies in (human) type 1 diabetes
SJ Bloem, BO Roep
Diabetologia 2017
Comparative and correlative assessments of cytokine, complement and antibody patterns in paediatric type 1 diabetes: Humoral immune patterns in pediatric T1D
M Abdel-Latif, AA Abdel-Moneim, MH El-Hefnawy, RG Khalil
Clinical & Experimental Immunology 2017
Publication trends of research on diabetes mellitus and T cells (1997–2016): A 20-year bibliometric study
Y Gao, Y Wang, X Zhai, Y He, R Chen, J Zhou, M Li, Q Wang, M Pietropaolo
PloS one 2017
T Cell-Mediated Chronic Inflammatory Diseases Are Candidates for Therapeutic Tolerance Induction with Heat Shock Proteins
AB Betancourt, Q Lyu, F Broere, A Sijts, VP Rutten, W Eden
Frontiers in immunology 2017
Translating Mechanism of Regulatory Action of Tolerogenic Dendritic Cells to Monitoring Endpoints in Clinical Trials
JS Suwandi, T Nikolic, BO Roep
Frontiers in immunology 2017
T Cell-Mediated Beta Cell Destruction: Autoimmunity and Alloimmunity in the Context of Type 1 Diabetes
AL Burrack, T Martinov, BT Fife
Frontiers in Endocrinology 2017
Type 1 diabetes genome-wide association studies: not to be lost in translation
F Pociot
IBMS BoneKEy 2017
Relapsing/remitting type 1 diabetes
KM van Megen, MP Spindler, FM Keij, I Bosch, F Sprangers, A van Royen-Kerkhof, T Nikolic, BO Roep
Diabetologia 2017
Beta-cell Specific Autoantibodies: Are they Just an Indicator of Type 1 Diabetes?
Fousteri G, Ippolito E, Ahmed R, Hamad ARA
Current diabetes reviews 2017

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