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1 型糖尿病中对 IL-2 的免疫耐受丧失。

Loss of immune tolerance to IL-2 in type 1 diabetes.

机构信息

Sorbonne Universités, Pierre and Marie Curie University Paris 06, Paris 75005, France.

Centre National de la Recherche Scientifique, UMR 7211, Paris 75013, France.

出版信息

Nat Commun. 2016 Oct 6;7:13027. doi: 10.1038/ncomms13027.

DOI:10.1038/ncomms13027
PMID:27708334
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5059699/
Abstract

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.

摘要

1 型糖尿病（T1D）的特征是慢性、进行性自身免疫攻击胰腺特异性抗原，导致胰岛素产生的β细胞破坏。在这里，我们表明白细胞介素 2（IL-2）是 T1D 中的非胰腺自身免疫靶标。非肥胖型糖尿病（NOD）小鼠和 T1D 患者的外周血中存在抗 IL-2 自身抗体以及针对 IL-2 单个同源表位的 T 细胞。在 NOD 小鼠中，抗 IL-2 自身抗体的产生是由遗传决定的，其滴度随年龄和疾病发作而增加。在 T1D 患者中，循环的针对 IL-2 或胰岛素的 IgG 记忆 B 细胞以相似的频率存在。从 T1D 患者中克隆的抗 IL-2 自身抗体显示出克隆性、高度体细胞超突变和纳摩尔亲和力，表明生发中心起源，并强调了同源自身反应性 T 和 B 细胞之间的协同作用，导致免疫耐受缺陷。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c0e/5059699/57557152000f/ncomms13027-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c0e/5059699/4f87d472331b/ncomms13027-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c0e/5059699/afef1b6eb5e8/ncomms13027-f2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c0e/5059699/7649466e4fef/ncomms13027-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c0e/5059699/615b105314ed/ncomms13027-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c0e/5059699/57557152000f/ncomms13027-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c0e/5059699/4f87d472331b/ncomms13027-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c0e/5059699/afef1b6eb5e8/ncomms13027-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c0e/5059699/63f24a976fcf/ncomms13027-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c0e/5059699/7649466e4fef/ncomms13027-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c0e/5059699/615b105314ed/ncomms13027-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c0e/5059699/57557152000f/ncomms13027-f6.jpg

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