TY - JOUR
T1 - Loss of immune tolerance to IL-2 in type 1 diabetes
AU - Pérol, Louis
AU - Lindner, John M.
AU - Caudana, Pamela
AU - Nunez, Nicolas Gonzalo
AU - Baeyens, Audrey
AU - Valle, Andrea
AU - Sedlik, Christine
AU - Loirat, Delphine
AU - Boyer, Olivier
AU - Créange, Alain
AU - Cohen, José Laurent
AU - Rogner, Ute Christine
AU - Yamanouchi, Jun
AU - Marchant, Martine
AU - Leber, Xavier Charles
AU - Scharenberg, Meike
AU - Gagnerault, Marie Claude
AU - Mallone, Roberto
AU - Battaglia, Manuela
AU - Santamaria, Pere
AU - Hartemann, Agnès
AU - Traggiai, Elisabetta
AU - Piaggio, Eliane
PY - 2016/10/6
Y1 - 2016/10/6
N2 - 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.
AB - 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.
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U2 - 10.1038/ncomms13027
DO - 10.1038/ncomms13027
M3 - Article
AN - SCOPUS:84990866020
VL - 7
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 13027
ER -