Cutting edge: CD4 T cells reactive to an islet amyloid polypeptide peptide accumulate in the pancreas and contribute to disease pathogenesis in nonobese diabetic mice.

Cutting edge: CD4 T cells reactive to an islet amyloid polypeptide peptide accumulate in the pancreas and contribute to disease pathogenesis in nonobese diabetic mice.
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DOI:
10.4049/jimmunol.1301480
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发表时间:
2013-10-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Haskins K
Haskins K
中科院分区:
其他
文献类型:
--
作者:
Baker RL;Delong T;Barbour G;Bradley B;Nakayama M;Haskins K

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我们之前报道了来自胰岛淀粉样多肽 (IAPP) 的肽 KS20 是高度致糖尿病的 CD4 T 细胞克隆 BDC-5.2.9 的靶抗原。为了追踪 NOD 小鼠中 IAPP 反应性 T 细胞并确定它们如何促进 1 型糖尿病 (T1D) 的发病机制,我们设计了一种新的 I-Ag7 四聚体,该四聚体对 BDC-5.2.9 具有高亲和力,其中包含肽 KS20。我们发现在糖尿病前期和糖尿病 NOD 小鼠的胰腺中可以检测到大量 KS20 四聚体阳性 CD4 T 细胞。为了验证 IAPP 反应细胞的致病性,从糖尿病小鼠脾脏和淋巴结中分离的未克隆 T 细胞系中分选并克隆了 KS20 四聚体阳性细胞。我们分离出一种新的 KS20 反应性 Th1 CD4 T 细胞克隆,可以快速转移糖尿病。我们的结果表明,IAPP 在 NOD 小鼠中通过 CD4 T 细胞触发广泛的自身免疫反应。
We previously reported a peptide KS20 from islet amyloid polypeptide (IAPP) to be the target antigen for a highly diabetogenic CD4 T cell clone BDC-5.2.9. In order to track IAPP-reactive T cells in NOD mice and determine how they contribute to the pathogenesis of type 1 diabetes (T1D), we designed a new I-Ag7 tetramer with high affinity for BDC-5.2.9 that contains the peptide KS20. We found that significant numbers of KS20 tetramer-positive CD4 T cells can be detected in the pancreas of pre-diabetic and diabetic NOD mice. To verify pathogenicity of IAPP-reactive cells, KS20 tetramer-positive cells were sorted and cloned from uncloned T cell lines isolated from spleen and lymph nodes of diabetic mice. We isolated a new KS20-reactive Th1 CD4 T cell clone that rapidly transfers diabetes. Our results suggest that IAPP triggers a broad autoimmune response by CD4 T cells in NOD mice.
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