| First Author | Pérol L | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 13027 | PubMed ID | 27708334 |
| Mgi Jnum | J:242356 | Mgi Id | MGI:5905081 |
| Doi | 10.1038/ncomms13027 | Citation | Perol L, et al. (2016) Loss of immune tolerance to IL-2 in type 1 diabetes. Nat Commun 7:13027 |
| abstractText | 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. |
