期刊
NATURE COMMUNICATIONS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms13027
关键词
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资金
- Ministere de la Recherche
- Ligue Nationale Contre le Cancer
- ARC [PJA 20131200444]
- Agence Nationale de la Recherche [ANR-09-GENO-006-01]
- EFSD/JDRF/NN
- INSERM/DGOS
- Inserm-Transfert and Aviesan/AstraZeneca 'Diabetes and the vessel wall injury' programme
- Canadian Institutes of Health Research
- Canadian Diabetes Association
Type 1 diabetes (T1D) is characterized by a chronic, progressive autoimmune attack against pancreas-specific antigens, effecting the destruction of insulin-producing beta-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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