UPMC Univ Paris 6, UMR_S938, Paris, France.
J Autoimmun. 2011 May;36(3-4):253-62. doi: 10.1016/j.jaut.2011.02.003. Epub 2011 Mar 17.
During pregnancy there is an exchange of cells between the fetus and the mother including T lymphocytes that can persist after delivery. Previous studies have described an increased numbers of maternal cells in children with juvenile diabetes as compared to their unaffected siblings. Our objective was to assess the possibility for these chimeric T cells to trigger an anti-beta cell response.
We mated OT2 transgenic female mice having T cells specifically targeting ovalbumin to RIP-OVA males expressing ovalbumin in pancreatic β cells. This allowed us to examine RIP-OVA progeny from OT2 mothers to assess the consequences of maternal T cells acquired during gestation or lactation. We quantitatively analyzed the pancreas of RIP-OVA mice from OT2 mothers for islet infiltration and compared them to RIP-OVA mice not exposed to OT2 mothers or to wild-type mice from OT2 mothers.
RIP-OVA mice from OT2 mothers had significantly more peri-insulitis (p=0.0083) compared to wild-type littermates. Similarly RIP-OVA mice from OT2 mothers had more peri-insulitis as compared to RIP-OVA mice from RIP-OVA mothers (p=0.0073). Presence and specific anti-ovalbumin activity of maternal OT2 cells in the offsprings' peripheral lymphoid tissues was found in a separate group of mice. In animals presenting islet inflammation, CD3+ infiltrating cells in the pancreas were however derived from the offspring and not from OT2 mothers. In accordance, OT2 and RIP-OVA double transgenic mice with high levels of auto-reactive T cells had more peri-insulitis and sometimes intense insulitis when they were from OT2 mothers as compared to RIP-OVA mothers (p=0.046).
In highly specific fetal/maternal combinations, maternal T cells with activity against the offspring pancreatic beta cells, presumably chimeric in fetal organs, initiate islet inflammation and may therefore predispose to auto-immune diabetes.
在妊娠期间，胎儿和母亲之间会发生细胞交换，包括 T 淋巴细胞，这些细胞在分娩后仍能持续存在。先前的研究表明，与未受影响的兄弟姐妹相比，患有青少年糖尿病的儿童的母亲细胞数量增加。我们的目的是评估这些嵌合 T 细胞是否有可能引发针对β细胞的反应。
我们将具有针对卵清蛋白的特异性 T 细胞的 OT2 转基因雌性小鼠与在胰腺β细胞中表达卵清蛋白的 RIP-OVA 雄性小鼠交配。这使我们能够检查来自 OT2 母亲的 RIP-OVA 后代，以评估在妊娠或哺乳期获得的母亲 T 细胞的后果。我们定量分析了来自 OT2 母亲的 RIP-OVA 小鼠的胰腺，以评估胰岛浸润情况，并将其与未接触 OT2 母亲的 RIP-OVA 小鼠或来自 OT2 母亲的野生型小鼠进行比较。
来自 OT2 母亲的 RIP-OVA 小鼠的胰岛周围炎明显更多（p=0.0083），与野生型同窝小鼠相比。同样，来自 OT2 母亲的 RIP-OVA 小鼠的胰岛周围炎也比来自 RIP-OVA 母亲的 RIP-OVA 小鼠更多（p=0.0073）。在另一组小鼠中发现，来自后代外周淋巴组织的母体 OT2 细胞存在且具有针对卵清蛋白的特异性活性。然而，在存在胰岛炎症的动物中，胰腺中浸润的 CD3+细胞来自后代，而不是来自 OT2 母亲。相应地，当来自 OT2 母亲时，具有高水平自身反应性 T 细胞的 OT2 和 RIP-OVA 双转基因小鼠的胰岛周围炎更多，有时甚至出现强烈的胰岛炎（p=0.046）。
在高度特异性的胎儿/母亲组合中，针对后代胰腺β细胞具有活性的母体 T 细胞，可能在胎儿器官中嵌合，会引发胰岛炎症，并因此可能导致自身免疫性糖尿病。
