Allergy prevention starts before conception: Maternofetal transfer of tolerance protects against the development of asthma
Allergy prevention starts before conception: Maternofetal transfer of tolerance protects against the development of asthma
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DOI：
10.1016/j.jaci.2008.09.014
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发表时间：
2008-11-01
影响因子：
14.2
通讯作者：
Hansen, Gesine
中科院分区：
文献类型：
--
作者：
Polte, Tobias;Hennig, Christian;Hansen, Gesine
工作背景：过敏预防必须尽早开始，因为环境暴露在怀孕期间和年轻的生命决定疾病risk.Objective：在这项研究中，我们分析了预防是否可以开始甚至更早的受孕前通过转移免疫耐受从母亲到后代，防止后代有asthma.Methods：BALB/c小鼠口服免疫耐受卵清蛋白受孕前通过口服应用抗原。在6周和4个月大时，用卵清蛋白免疫耐受和幼稚母亲的后代，并在我们的小鼠哮喘模型中进行分析。结果：尽管幼稚母亲的后代具有哮喘样表型，但耐受小鼠的后代即使在出生后8个月免疫，也得到了完全保护。过敏原特异性IgG在耐受性转移中起关键作用，其水平在母体、胎儿、幼仔和母乳的血清中升高。FcRn（-/-）小鼠不能通过胎盘转运IgG，仅当缺失的胎盘IgG转移被耐受性母亲通过母乳的IgG转移补偿时，才将耐受性转移给后代，但当由幼稚的奶妈断奶时则不然。抑制IFN-γ，产生的记忆T细胞在后代中，废除了母体耐受性的保护作用，表现出一个至关重要的作用，IFN-γ在维持过敏原特异性tolerance.Conclusion：我们的数据表明，母亲的免疫记忆有一个显着的和持久的影响后代的免疫反应。（J Allergy Clin Immunol 2008;122：1022-30.）
Background: Allergy prevention must start early because environmental exposures during pregnancy and young life determine disease risk.Objective: In this study we analyzed whether prevention can start even earlier before conception by transfer of immunologic tolerance from the mother to the offspring preventing the offspring from having asthma.Methods: BALB/c mice were orally tolerized with ovalbumin before conception by means of oral application of antigen. The offspring of tolerized and naive mothers were immunized with ovalbumin at 6 weeks and 4 months of age and analyzed in our murine asthma model.Results: Although the offspring of naive mothers had an asthma-like phenotype, the offspring of tolerized mice were completely protected, even when immunized as late as 8 months after birth. Critically involved in the tolerance transfer was allergen-specific IgG, levels of which were increased in the sera of the mother, fetus, and pup and breast milk. FcRn(-/-) mice, which cannot transport IgG through the placenta, transferred tolerance to the offspring only when the missing diaplacental IgG transfer was compensated by IgG transfer through breast milk from tolerant mothers but not when weaned by naive wet nurses. Inhibition of IFN-gamma, produced by memory T cells in the offspring, abrogated the protective effect of maternal tolerance, demonstrating a crucial role for IFN-gamma in the maintenance of allergen-specific tolerance.Conclusion: Our data show that maternal immunologic memory has a significant and persistent effect on the immune response of the offspring. (J Allergy Clin Immunol 2008;122:1022-30.)