The healthy exocrine pancreas contains preproinsulin-specific CD8 T cells that attack islets in type 1 diabetes.
The healthy exocrine pancreas contains preproinsulin-specific CD8 T cells that attack islets in type 1 diabetes.
复制标题
DOI：
10.1126/sciadv.abc5586
复制
发表时间：
2020-10
期刊：
影响因子：
13.6
通讯作者：
von Herrath MG
中科院分区：
文献类型：
--
作者：
Bender C;Rodriguez-Calvo T;Amirian N;Coppieters KT;von Herrath MG
前胰岛素原特异性CD8+ T细胞驻留在胰腺外分泌成为1型糖尿病胰岛吸引。前胰岛素原（PPI）可能是1型糖尿病（T1D）患者中发现的重要胰岛自身抗原，但也被健康个体的CD8+ T细胞识别。我们定量了非糖尿病对照组、自身抗体阳性供体和T1D供体胰腺不同区域的PPI特异性CD8+ T细胞，以研究其在糖尿病发展中的作用。这种空间细胞定量显示自身反应性CD8+ T细胞的频率异常高，支持PPI确实是一种关键自身抗原的假设。令我们惊讶的是，PPI特异性CD8+ T细胞已经大量存在于非糖尿病胰腺中，从而质疑T1D是由缺陷性胸腺缺失或系统性免疫失调引起的教条。在T1D发育过程中，这些细胞在胰岛内和周围积累，表明胰岛特异性触发因子，如I类主要组织相容性复合物的上调，可能对免疫系统暴露β细胞至关重要。
Preproinsulin-specific CD8+ T cells residing in the exocrine pancreas become attracted to islets in type 1 diabetes. Preproinsulin (PPI) is presumably a crucial islet autoantigen found in patients with type 1 diabetes (T1D) but is also recognized by CD8+ T cells from healthy individuals. We quantified PPI-specific CD8+ T cells within different areas of the human pancreas from nondiabetic controls, autoantibody-positive donors, and donors with T1D to investigate their role in diabetes development. This spatial cellular quantitation revealed unusually high frequencies of autoreactive CD8+ T cells supporting the hypothesis that PPI is indeed a key autoantigen. To our surprise, PPI-specific CD8+ T cells were already abundantly present in the nondiabetic pancreas, thus questioning the dogma that T1D is caused by defective thymic deletion or systemic immune dysregulation. During T1D development, these cells accumulated in and around islets, indicating that an islet-specific trigger such as up-regulation of major histocompatibility complex class I might be essential to unmask beta cells to the immune system.
登录
查看更多内容
影响因子：
7.3
作者：
Benechet AP;Menon M;Khanna KM
通讯作者：
Khanna KM
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
4.4
作者：
Chee, Jonathan;Ko, Hyun-Ja;Krishnamurthy, Balasubramanian
通讯作者：
Krishnamurthy, Balasubramanian
影响因子：
8.2
作者：
Richardson, Sarah J.;Rodriguez-Calvo, Teresa;Gerling, Ivan C.;Mathews, Clayton E.;Kaddis, John S.;Russell, Mark A.;Zeissler, Marie;Leete, Pia;Krogvold, Lars;Dahl-Jorgensen, Knut;von Herrath, Matthias;Pugliese, Alberto;Atkinson, Mark A.;Morgan, Noel G.
通讯作者：
Morgan, Noel G.
影响因子：
3.4
作者：
Li X;Atkinson MA
通讯作者：
Atkinson MA