Physiological and pathogenic T cell autoreactivity converge in type 1 diabetes.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
29 Oct 2024
29 Oct 2024
Historique:
received:
30
01
2024
accepted:
08
10
2024
medline:
30
10
2024
pubmed:
30
10
2024
entrez:
30
10
2024
Statut:
epublish
Résumé
Autoimmune diseases result from autoantigen-mediated activation of adaptive immunity; intriguingly, autoantigen-specific T cells are also present in healthy donors. An assessment of dynamic changes of this autoreactive repertoire in both health and disease is thus warranted. Here we investigate the physiological versus pathogenic autoreactive processes in the context of Type 1 diabetes (T1D) and one of its landmark autoantigens, glutamic acid decarboxylase 65 (GAD65). Using single cell gene expression profiling and tandem T cell receptor (TCR) sequencing, we find that GAD65-specific true naïve cells are present in both health and disease, with GAD65-specific effector and memory responses showing similar ratios in healthy donors and patients. Deeper assessment of phenotype and TCR repertoire uncover differential features in GAD65-specific TCRs, including lower clonal sizes of healthy donor-derived clonotypes in patients. We thus propose a model whereby physiological autoimmunity against GAD65 is needed during early life, and that alterations of these physiological autoimmune processes in predisposed individuals trigger overt Type 1 diabetes.
Identifiants
pubmed: 39472557
doi: 10.1038/s41467-024-53255-9
pii: 10.1038/s41467-024-53255-9
doi:
Substances chimiques
Glutamate Decarboxylase
EC 4.1.1.15
glutamate decarboxylase 2
EC 4.1.1.15
Receptors, Antigen, T-Cell
0
Autoantigens
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9204Subventions
Organisme : Xunta de Galicia
ID : ED431C 2023/28
Organisme : EC | EC Seventh Framework Programm | FP7 People: Marie-Curie Actions (FP7-PEOPLE - Specific Programme "People" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))
ID : PIEF-GA-2012-327908
Organisme : Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia (Ministry of Culture, Education and University Planning, Government of Galicia)
ID : ED481A 2022/422
Informations de copyright
© 2024. The Author(s).
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