Loss of immune tolerance to IL-2 in type 1 diabetes

Louis Pérol, John M. Lindner, Pamela Caudana, Nicolas Gonzalo Nunez, Audrey Baeyens, Andrea Valle, Christine Sedlik, Delphine Loirat, Olivier Boyer, Alain Créange, José Laurent Cohen, Ute Christine Rogner, Jun Yamanouchi, Martine Marchant, Xavier Charles Leber, Meike Scharenberg, Marie-Claude Gagnerault, Roberto Mallone, Manuela Battaglia, Pere Santamaria, Agnès Hartemann, Elisabetta Traggiai and Eliane Piaggio ()
Additional contact information
Louis Pérol: Sorbonne Universités, Pierre and Marie Curie University Paris 06
John M. Lindner: Novartis Institutes for Biomedical Research
Pamela Caudana: Institut Curie, PSL Research University, INSERM U932
Nicolas Gonzalo Nunez: Institut Curie, PSL Research University, INSERM U932
Audrey Baeyens: Sorbonne Universités, Pierre and Marie Curie University Paris 06
Andrea Valle: Diabetes Research Institute (DRI), IRCCS San Raffaele Scientific Institute
Christine Sedlik: Institut Curie, PSL Research University, INSERM U932
Delphine Loirat: SiRIC TransImm Translational Immunotherapy Team, Research Center, PSL Research University, Institut Curie
Olivier Boyer: INSERM, U905
Alain Créange: Service de Neurologie, Groupe Hospitalier Henri Mondor, AP-HP
José Laurent Cohen: Université Paris-Est Créteil
Ute Christine Rogner: Institut Pasteur, CNRS URA 2578
Jun Yamanouchi: Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, Cumming School of Medicine. University of Calgary
Martine Marchant: Novartis Institutes for Biomedical Research
Xavier Charles Leber: Novartis Institutes for Biomedical Research
Meike Scharenberg: Novartis Institutes for Biomedical Research
Marie-Claude Gagnerault: INSERM, U1016, Cochin Institute, DeAR Lab
Roberto Mallone: INSERM, U1016, Cochin Institute, DeAR Lab
Manuela Battaglia: Diabetes Research Institute (DRI), IRCCS San Raffaele Scientific Institute
Pere Santamaria: Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, Cumming School of Medicine. University of Calgary
Agnès Hartemann: Université Pierre et Marie Curie—Paris 6
Elisabetta Traggiai: Novartis Institutes for Biomedical Research
Eliane Piaggio: Sorbonne Universités, Pierre and Marie Curie University Paris 06

Nature Communications, 2016, vol. 7, issue 1, 1-10

Abstract: Abstract Type 1 diabetes (T1D) is characterized by a chronic, progressive autoimmune attack against pancreas-specific antigens, effecting the destruction of insulin-producing β-cells. Here we show interleukin-2 (IL-2) is a non-pancreatic autoimmune target in T1D. Anti-IL-2 autoantibodies, as well as T cells specific for a single orthologous epitope of IL-2, are present in the peripheral blood of non-obese diabetic (NOD) mice and patients with T1D. In NOD mice, the generation of anti-IL-2 autoantibodies is genetically determined and their titre increases with age and disease onset. In T1D patients, circulating IgG memory B cells specific for IL-2 or insulin are present at similar frequencies. Anti-IL-2 autoantibodies cloned from T1D patients demonstrate clonality, a high degree of somatic hypermutation and nanomolar affinities, indicating a germinal centre origin and underscoring the synergy between cognate autoreactive T and B cells leading to defective immune tolerance.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms13027 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13027

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms13027

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().