Pregnancy-induced transfer of pathogen-specific T cells from mother to fetus in mice

Neonatal health is determined by the transfer of maternal antibodies from the mother to the fetus. Besides antibodies, maternal cells cross the placental barrier and seed into fetal organs. Contrary to maternal antibodies, maternal microchimeric cells (MMc) show a high longevity, as they can persist in the offspring until adulthood. Recent evidence highlights that MMc leukocytes promote neonatal immunity against early-life infections in mice and humans. As shown in mice, this promotion of immunity was attributable to an improved fetal immune development. Besides this indirect effect, MMc may be pathogen-specific and thus, directly clear pathogen threats in the offspring postnatally. By using ovalbumin recombinant L. monocytogenes (LmOVA), we here provide evidence that OVA-specific T cells are transferred from the mother to the fetus, which is associated with increased activation of T cells and a milder course of postnatal infection in the offspring. Our data highlight that maternally-derived passive immunity of the neonate is not limited to antibodies, as MMc have the potential to transfer immune memory between generations.

新生儿健康由母体抗体向胎儿的转运所决定。除抗体外，母体细胞可穿越胎盘屏障并定植于胎儿器官。与母体抗体不同，母体微嵌合细胞（maternal microchimeric cells, MMc）寿命持久，可在子代体内持续存在至成年阶段。最新研究证据表明，MMc白细胞可促进小鼠与人类新生儿抵御早期感染的免疫能力。正如小鼠实验所证实，此种免疫促进效应源于胎儿免疫发育的改善。除上述间接作用外，MMc还可表现出病原体特异性，从而在子代出生后直接清除体内的病原体威胁。本研究采用卵清蛋白重组单核细胞增生李斯特菌（ovalbumin recombinant L. monocytogenes, LmOVA），证实了卵清蛋白特异性T细胞可由母体向胎儿转运，该过程与子代T细胞激活水平升高以及产后感染病程减轻密切相关。本研究数据显示，新生儿的母源被动免疫并非仅局限于抗体，因MMc具备在代际间传递免疫记忆的潜力。