Human Type 1 Diabetes Is Associated with T Cell Autoimmunity to Zinc Transporter 8
Open Access
- 15 May 2011
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 186 (10), 6056-6063
- https://doi.org/10.4049/jimmunol.1003815
Abstract
Recently we demonstrated that zinc transporter 8 (ZnT8) is a major target of autoantibodies in human type 1 diabetes (T1D). Because the molecules recognized by T1D autoantibodies are typically also targets of autoreactive T cells, we reasoned that this would likely be the case for ZnT8. To test this hypothesis, IFN-γ–producing T cells specific for ZnT8 in the peripheral blood of 35 patients with T1D (p < 0.0001) for the patients. Similarly, the median stimulation index of positive responses in controls was 3.1 versus 5.0 in the patients (p < 0.0001). Individually, 7 of 23 pools showed significant disease association (p < 0.001), with several of the component peptides binding the disease associated HLA-DR3 (0301) and -DR4 (0401) molecules in vitro. We conclude that ZnT8 is also a major target of disease-associated autoreactive T cells in human T1D, and we suggest that reagents that target ZnT8-specific T cells could have therapeutic potential in preventing or arresting the progression of this disease.Keywords
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