Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 751 85, Uppsala, Sweden.
Department of Medical Sciences, Section of Clinical Microbiology, Uppsala University, Uppsala, Sweden.
Acta Diabetol. 2022 Aug;59(8):1011-1018. doi: 10.1007/s00592-022-01881-4. Epub 2022 Apr 24.
Periductal inflammation and accumulation of granulocytes and monocytes in the periislet area and in the exocrine pancreas is observed within hours after instillation of heat-inactivated bacteria in the ductal compartment of the pancreas in healthy rats. The present investigation was undertaken to study how the acute inflammation developed over time.
Immunohistochemical evaluation of the immune response triggered by instillation of heat-inactivated bacteria in the ductal compartment in rats.
After three weeks, the triggered inflammation had vanished and pancreases showed normal morphology. However, a distinct accumulation of both CD4+ and CD8+ T cells within and adjacent to affected islets was found in one-third of the rats instilled with heat-inactivated E. faecalis, mimicking the insulitis seen at onset of human T1D. As in T1D, this insulitis affected a minority of islets and only certain lobes of the pancreases. Notably, a fraction of the T cells expressed the CD103 antigen, mirroring the recently reported presence of tissue resident memory T cells in the insulitis in humans with recent onset T1D.
The results presented unravel a previously unknown interplay between innate and acquired immunity in the formation of immunopathological events indistinguishable from those described in humans with recent onset T1D.
在健康大鼠的胰腺导管腔内注入热灭活细菌后数小时内，可观察到导管周围区域和胰岛周围区域的炎症和粒细胞及单核细胞的聚集。本研究旨在研究急性炎症随时间的发展情况。
免疫组织化学评价热灭活细菌注入导管腔后引发的免疫反应。
3 周后，触发的炎症已消失，胰腺呈现正常形态。然而，在三分之一接受热灭活粪肠球菌注入的大鼠中，发现 CD4+和 CD8+T 细胞在受影响的胰岛内和周围明显聚集，类似于人类 T1D 发病时的胰岛炎。与 T1D 一样，这种胰岛炎影响少数胰岛，仅影响胰腺的某些叶。值得注意的是，一部分 T 细胞表达 CD103 抗原，反映了最近在人类 T1D 发病时的胰岛炎中存在组织驻留记忆 T 细胞。
本研究结果揭示了先天免疫和获得性免疫之间以前未知的相互作用，形成了与人类近期发病的 T1D 中描述的免疫病理事件难以区分的免疫病理事件。
