Maternal Milk T Cells Drive Development of Transgenerational Th1 Immunity in Offspring Thymus
Maternal Milk T Cells Drive Development of Transgenerational Th1 Immunity in Offspring Thymus
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DOI：
10.4049/jimmunol.1502483
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发表时间：
2016-09-15
影响因子：
4.4
通讯作者：
Walker, Ameae M.
中科院分区：
文献类型：
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作者：
Ghosh, Mrinal K.;Nguyen, Virginia;Walker, Ameae M.
使用多种小鼠培养护理方案，从而消除胎盘移植，并允许区分母鼠和幼崽来源的细胞，我们表明，免疫母鼠的培养护理导致未免疫的培养幼崽中CD8(+) T细胞的发育，这些细胞对培养母鼠免疫的Ags（结核分枝杆菌或白色念珠菌）具有特异性。我们将这一过程称为“母体教育免疫”，以区别于被动细胞免疫。在乳汁中存在的多种母体免疫细胞中，只有T细胞在幼犬组织中被检测到。母性T细胞，其中CD4(+)MHC II+类占很大比例，在哺乳期间积聚在幼犬胸腺和脾脏。对幼犬胸腺母系细胞的进一步分析表明，一定比例的母系免疫原特异性MHC II类四聚体呈阳性。为了确定银在胸腺内呈递的结果，我们评估了母鼠或寄养幼犬脾脏中免疫原应答CD8（+）细胞的来源。在断奶后的最初几周内，母鼠获得了大约10%的CD8(+) T细胞，所有免疫原应答的CD8(+) T细胞都是在12周龄时获得的。幼犬衍生的免疫原反应性CD8（+）细胞至少持续到1岁。被动细胞免疫已被广泛接受，并已在人群中得到证实。在这项研究中，我们展示了转移免疫细胞的一个更重要的作用：后代T细胞发育的方向。通过孕前免疫规划利用孕产妇教育免疫，有可能提高婴儿免疫力。
Using multiple murine foster-nursing protocols, thereby eliminating placental transfer and allowing a distinction between dam and pup-derived cells, we show that foster nursing by an immunized dam results in development of CD8(+) T cells in non immunized foster pups that are specific for Ags against which the foster dam was immunized (Mycobacterium tuberculosis or Candida albicans). We have dubbed this process "maternal educational immunity" to distinguish it from passive cellular immunity. Of the variety of maternal immune cells present in milk, only T cells were detected in pup tissues. Maternal T cells, a substantial percentage of which were CD4(+)MHC class II+, accumulated in the pup thymus and spleen during the nursing period. Further analysis of maternal cells in the pup thymus showed that a proportion was positive for maternal immunogen-specific MHC class II tetramers. To determine the outcome of Ag presentation in the thymus, the maternal or foster pup origin of immunogen-responding CD8(+) cells in foster pup spleens was assessed. Whereas similar to 10% were maternally derived in the first few weeks after weaning, all immunogen-responding CD8(+) T cells were pup derived by 12 wk of age. Pup derived immunogen-responsive CD8(+) cells persisted until at least 1 y of age. Passive cellular immunity is well accepted and has been demonstrated in the human population. In this study, we show an arguably more important role for transferred immune cells: the direction of offspring T cell development. Harnessing maternal educational immunity through prepregnancy immunization programs has potential for improvement of infant immunity.