UMDNJ - New Jersey Medical School and Graduate School of Biomedical Sciences, Newark, NJ 07101, USA.
J Reprod Immunol. 2010 Dec;87(1-2):97-100. doi: 10.1016/j.jri.2010.06.156. Epub 2010 Aug 19.
Pregnant mice were stimulated at day 12 of gestation with the nucleotide poly(I:C). At 24h after stimulation, serum levels of maternal cytokines were measured, and at postnatal ages 2 and 3 weeks, offspring were analyzed for T helper (Th) cell subsets. Lymphocytes from offspring of poly(I:C)-injected (vs. control PBS-injected) pregnant dams preferentially developed into T helper 17 (Th17) cells upon in vitro activation. This occurred in offspring of pregnant dams who exhibited an immunological "memory" phenotype, but not in offspring of immunologically "naïve" dams. Preferential development of Th17 cells in these offspring may be facilitated by the higher levels of pro-inflammatory cytokines such as IL-6, found in immune vs. naïve pregnant dams. Murine immune stimulation during pregnancy is frequently used to model human neurological disorders, such as autism and schizophrenia. However, immune stimulation of women during pregnancy occurs in the context of an immunological "memory" phenotype, resulting from previous immunizations and/or natural exposure to micro-organisms and other antigens. Therefore, use of previously immunized female mice with a similar immunological memory phenotype to study maternal immune stimulation during pregnancy presents a more biologically relevant experimental strategy to investigate developmental, behavioral, and immunological sequelae of offspring in such rodent models.
妊娠 12 天的小鼠用核苷酸 poly(I:C)刺激。刺激后 24 小时测量母鼠细胞因子的血清水平,在产后 2 周和 3 周时,分析子代的 T 辅助(Th)细胞亚群。与对照 PBS 注射的孕鼠相比,poly(I:C) 注射的孕鼠的子代淋巴细胞在体外激活时更倾向于发育为 Th17(Th17)细胞。这种情况发生在具有免疫“记忆”表型的孕鼠的子代中,但在免疫“幼稚”的孕鼠的子代中没有发生。在这些子代中,Th17 细胞的优先发育可能是由免疫母鼠中更高水平的促炎细胞因子(如 IL-6)促进的,而在幼稚母鼠中则没有。在妊娠期间对小鼠进行免疫刺激常用于模拟人类神经紊乱,如自闭症和精神分裂症。然而,妊娠期间女性的免疫刺激发生在免疫“记忆”表型的背景下,这是由于以前的免疫接种和/或自然暴露于微生物和其他抗原。因此,使用具有类似免疫记忆表型的先前免疫的雌性小鼠来研究妊娠期间的母体免疫刺激,是研究此类啮齿动物模型中后代发育、行为和免疫后果的更具生物学相关性的实验策略。