Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
Department of Obstetrics and Gynecology, University of Granada, Granada, Spain.
Immunology. 2021 Jul;163(3):338-343. doi: 10.1111/imm.13321. Epub 2021 Mar 22.
Humanized double transgenic mice express both HLA-DR15 (the MHC gene linked to MS) and TCR.Ob1A12 from a multiple sclerosis patient (that recognizes MBP85-99 presented by HLA-DR15), yet they fail to develop autoimmune encephalomyelitis quickly, although 5-10% develop disease at 12 months. These mice were found to express large numbers of IL-10-secreting splenocytes as early as 4 weeks of age. These regulatory T cells appeared spontaneously without prior immunization with the autoantigen MBP85-99. They were of murine origin and had a cytokine secretion profile and surface phenotype similar to that reported for Tr1 cells. Notably, the frequency of disease appeared to increase at 14 months. The diseased mice had small spleens which averaged 47 mg, while the remaining non-diseased mice in our colony killed at ages 14-15 months had splenocytes that averaged 80 mg (ranging from 47-130 mg). Thus, the appearance of disease was associated with diminution in numbers of IL-10-secreting regulatory T cells with age.
人源化双转基因小鼠表达 HLA-DR15（与 MS 相关的 MHC 基因）和 TCR.Ob1A12，后者来自一位多发性硬化症患者（可识别由 HLA-DR15 呈递的 MBP85-99），但它们未能迅速发展出自免疫性脑脊髓炎，尽管有 5-10%的小鼠在 12 个月时发病。这些小鼠早在 4 周龄时就被发现表达大量分泌 IL-10 的脾细胞。这些调节性 T 细胞在没有预先用自身抗原 MBP85-99 免疫的情况下自发出现。它们来源于鼠类，细胞因子分泌谱和表面表型与报道的 Tr1 细胞相似。值得注意的是，疾病的频率似乎在 14 个月时增加。患病小鼠的脾脏较小，平均为 47mg，而我们群体中在 14-15 个月龄时死亡的其余未患病小鼠的脾细胞平均为 80mg（范围为 47-130mg）。因此，疾病的出现与年龄相关的分泌 IL-10 的调节性 T 细胞数量减少有关。
