Frankel Laboratory, Centre for Stem Cell Research, Schneider Children's Medical Centre of Israel, Petach Tikva, Israel; Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Immunology. 2014 Jul;142(3):465-73. doi: 10.1111/imm.12277.
The non-obese diabetic (NOD) mouse is a prevalent disease model of type 1 diabetes. Immune aberrations that cause and propagate autoimmune insulitis in these mice are being continually debated, with evidence supporting both dominance of effector cells and insufficiency of suppressor mechanisms. In this study we assessed the behaviour of NOD lymphocytes under extreme expansion conditions using adoptive transfer into immunocompromised NOD.SCID (severe combined immunodeficiency) mice. CD4(+) CD25(+) T cells do not cause islet inflammation, whereas splenocytes and CD4(+) CD25(-) T cells induce pancreatic inflammation and hyperglycaemia in 80-100% of the NOD.SCID recipients. Adoptively transferred effector T cells migrate to the lymphoid organs and pancreas, proliferate, are activated in the target organ in situ and initiate inflammatory insulitis. Reconstitution of all components of the CD4(+) subset emphasizes the plastic capacity of different cell types to adopt effector and suppressor phenotypes. Furthermore, similar immune profiles of diabetic and euglycaemic NOD.SCID recipients demonstrate dissociation between fractional expression of CD25 and FoxP3 and the severity of insulitis. There were no evident and consistent differences in diabetogenic activity and immune reconstituting activity of T cells from pre-diabetic (11 weeks) and new onset diabetic NOD females. Similarities in immune phenotypes and variable distribution of effector and suppressor subsets in various stages of inflammation commend caution in interpretation of quantitative and qualitative aberrations as markers of disease severity in adoptive transfer experiments.
非肥胖型糖尿病（NOD）小鼠是 1 型糖尿病的常见疾病模型。导致这些小鼠自身免疫性胰岛炎的免疫异常仍在不断争论中，有证据表明效应细胞占主导地位和抑制机制不足。在这项研究中，我们通过将 NOD 淋巴细胞过继转移到免疫缺陷 NOD.SCID（严重联合免疫缺陷）小鼠中来评估其在极端扩增条件下的行为。CD4(+)CD25(+)T 细胞不会引起胰岛炎症，而脾细胞和 CD4(+)CD25(-)T 细胞在 80-100%的 NOD.SCID 受体中引起胰腺炎症和高血糖。过继转移的效应 T 细胞迁移到淋巴器官和胰腺，增殖，在靶器官原位激活，并引发炎症性胰岛炎。CD4(+)亚群的所有成分的重建强调了不同细胞类型具有采用效应和抑制表型的可塑性能力。此外，糖尿病和血糖正常的 NOD.SCID 受体的相似免疫特征表明 CD25 和 FoxP3 的分数表达与胰岛炎的严重程度之间存在分离。来自糖尿病前期（11 周）和新发糖尿病 NOD 雌性的 T 细胞的致糖尿病活性和免疫重建活性没有明显和一致的差异。在炎症的各个阶段，免疫表型的相似性和效应和抑制亚群的可变分布证明在过继转移实验中，定量和定性异常作为疾病严重程度的标志物的解释需要谨慎。
