Department of Environmental Immunology, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway.
BMC Immunol. 2010 Mar 1;11:8. doi: 10.1186/1471-2172-11-8.
Allergy has been an increasing problem in several parts of the world. Prenatal exposure to allergen and microbial components may affect the development of allergies in childhood, as indicated by epidemiological and experimental studies. We investigated the capacity for allergic sensitisation in offspring after induction of a Th1- or a Th2-polarised immune response to the same allergen in mothers during pregnancy.
During pregnancy, mice were immunised with ovalbumin (OVA) given with either one of the Th2-adjuvants pertussis toxin (PT) or Al(OH)3 (aluminium hydroxide), or with the Th1 adjuvant CpG. Offspring were immunised with OVA in Al(OH)3 as young adults. Serum and supernatants from ex vivo stimulated or non-stimulated spleen cells from mothers and offspring were analysed for OVA-specific antibodies and cytokines, respectively. Mothers immunised with OVA together with either Al(OH)3 or PT had increased levels of OVA-specific IgE and IgG1 compared to naive mothers, whereas mothers immunised with OVA together with CpG had increased levels of OVA-specific IgG2a compared to naive mothers. In general the highest levels of IL-5, IL-10, and IFNgamma were observed in spleen cells from mothers immunised with PT and OVA. Upon immunisation, offspring from mothers immunised with OVA and either PT or Al(OH)3 showed reduced levels of OVA-specific IgE and IgG1 and increased levels of OVA-specific IgG2a antibodies compared to offspring from naive mothers. Maternal immunisation with CpG and OVA did not affect antibody responses in offspring.
Allergic sensitisation in the offspring was affected by the type of adjuvant used for immunisation of the mothers with the same allergen. Th2 polarisation of the immune response in the mothers was found to give reduced IgE levels upon sensitisation of the offspring, whereas no reduction was achieved with Th1 polarisation in the mothers.
过敏已成为世界上许多地区日益严重的问题。产前接触过敏原和微生物成分可能会影响儿童时期过敏的发展,这一点已被流行病学和实验研究表明。我们研究了在母亲怀孕期间用相同过敏原诱导 Th1 或 Th2 极化免疫应答后,其后代发生过敏敏化的能力。
在怀孕期间,用百日咳毒素(PT)或氢氧化铝(Al(OH)3)佐剂中的一种或 Th1 佐剂 CpG 与卵清蛋白(OVA)一起对小鼠进行免疫接种。后代在成年时用 Al(OH)3 中的 OVA 进行免疫接种。分析母亲和后代的经体外刺激或未经刺激的脾细胞的血清和上清液,以分别检测 OVA 特异性抗体和细胞因子。与未致敏的母亲相比,用 OVA 与 Al(OH)3 或 PT 一起免疫接种的母亲的 OVA 特异性 IgE 和 IgG1 水平增加,而用 OVA 与 CpG 一起免疫接种的母亲的 OVA 特异性 IgG2a 水平增加。通常,PT 和 OVA 免疫接种的母亲脾细胞中观察到的 IL-5、IL-10 和 IFNγ 水平最高。在免疫接种时,与来自未致敏母亲的后代相比,来自用 OVA 和 PT 或 Al(OH)3 免疫接种的母亲的后代的 OVA 特异性 IgE 和 IgG1 水平降低,而 OVA 特异性 IgG2a 抗体水平升高。用 CpG 和 OVA 对母亲进行免疫接种不会影响后代的抗体反应。
用于母亲免疫接种的佐剂类型会影响后代的过敏敏化。在母亲中诱导 Th2 极化免疫应答会导致后代致敏时 IgE 水平降低,而在母亲中诱导 Th1 极化则无法实现这种降低。