Open AccessLoss of immune tolerance to IL-2 in type 1 diabetes
Author(s) -
Louis Pérol,
John M. Lindner,
Pamela Caudana,
Nicolás Gonzalo Núñez,
Audrey Baeyens,
Andrea Valle,
Christine Sedlik,
Delphine Loirat,
Olivier Boyer,
Alain Créange,
José L. Cohen,
Ute Christine Rogner,
Jun Yamanouchi,
Martine Marchant,
Xavier Charles Leber,
Meike Scharenberg,
MarieClaude Gagnerault,
Roberto Mallone,
Manuela Battaglia,
Pere Santamaría,
A. Hartemann,
Elisabetta Traggiai,
Eliane Piaggio
Publication year - 2016
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/ncomms13027
Subject(s) - type 2 diabetes , immune system , diabetes mellitus , immune tolerance , type 1 diabetes , medicine , immunology , biology , endocrinology
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.