Human type 1 diabetes is associated with T cell autoimmunity to zinc transporter 8.
Human type 1 diabetes is associated with T cell autoimmunity to zinc transporter 8.
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DOI：
10.4049/jimmunol.1003815
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发表时间：
2011-05-15
期刊：
影响因子：
--
通讯作者：
Davidson HW
中科院分区：
文献类型：
--
作者：
Dang M;Rockell J;Wagner R;Wenzlau JM;Yu L;Hutton JC;Gottlieb PA;Davidson HW
Recently we demonstrated that zinc transporter 8 (ZnT8) is a major target of autoantibodies in human type 1 diabetes (T1D). Since 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 (< 6mo post-onset at blood draw) and 41 age-matched controls were assayed by ELISPOT using a library of 23 overlapping di-peptide pools covering the entire 369aa primary sequence. Consistent with our hypothesis, patients showed significantly higher T cell reactivity than the matched controls, manifest both in terms of the breadth of the overall response, and the magnitude of responses to individual pools. Thus, the median number of pools giving positive responses (stimulation index ≥ 3) in the control group was 1.0 (range 0 – 7) compared to 6.0 (range 1 – 20; p < 0.0001) for the patients. Similarly, the median SI of positive responses in controls was 3.1 versus 5.0 in the patients (p < 0.0001). Individually 7/23 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 suggest that reagents that target ZnT8-specific T cells may have therapeutic potential in preventing or arresting the progression of this disease.
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影响因子：
9.1
作者：
Ott, PA;Dittrich, MT;Lehmann, PV
通讯作者：
Lehmann, PV
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Brooks-Worrell, Barbara;Warsen, Adelaide;Palmer, Jerfy P.
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Ziegler, A. G.
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Eguchi, K.
影响因子：
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作者：
Chimienti, F;Devergnas, S;Seve, M
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Seve, M