Ghosh Mrinal K, Nguyen Virginia, Muller H Konrad, Walker Ameae M
Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA 92521; and.
School of Medicine, University of Tasmania, Hobart, Tasmania 7000, Australia.
J Immunol. 2016 Sep 15;197(6):2290-6. doi: 10.4049/jimmunol.1502483. Epub 2016 Aug 5.
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 nonimmunized 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 ∼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.
通过使用多种小鼠代乳方案,从而消除胎盘转移并区分母源和幼崽源细胞,我们发现由免疫母鼠进行代乳会导致未免疫的代养幼崽中发育出针对母鼠所免疫抗原(结核分枝杆菌或白色念珠菌)的CD8(+) T细胞。我们将这一过程称为“母源性教育免疫”,以区别于被动细胞免疫。在乳汁中存在的多种母源免疫细胞中,仅在幼崽组织中检测到了T细胞。母源T细胞在哺乳期间积聚在幼崽的胸腺和脾脏中,其中很大一部分是CD4(+)MHC II类(+)。对幼崽胸腺中的母源细胞进行进一步分析表明,一部分细胞对母源免疫原特异性MHC II类四聚体呈阳性。为了确定胸腺中抗原呈递的结果,评估了代养幼崽脾脏中对免疫原作出反应的CD8(+)细胞的母源或代养幼崽来源。断奶后的最初几周内,约10%的细胞源自母源,而到12周龄时,所有对免疫原作出反应的CD8(+) T细胞均源自幼崽。幼崽来源的对免疫原作出反应的CD8(+)细胞至少持续存在到1岁。被动细胞免疫已被广泛接受,并已在人类中得到证实。在本研究中,我们展示了转移免疫细胞一个可能更重要的作用:后代T细胞发育的导向。通过孕前免疫计划利用母源性教育免疫具有改善婴儿免疫力的潜力。
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