Th1/Th2 patterns and balance in cytokine production in the parents and infants of a large birth cohort.

Th1/Th2 patterns and balance in cytokine production in the parents and infants of a large birth cohort.
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DOI:
10.4049/jimmunol.0711996
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发表时间:
2009-03-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Wright AL
Wright AL
中科院分区:
其他
文献类型:
--
作者:
Halonen M;Lohman IC;Stern DA;Spangenberg A;Anderson D;Mobley S;Ciano K;Peck M;Wright AL

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体内人免疫细胞细胞因子产生的调节尚未得到很好的理解,部分原因是对实验条件的限制。我们提出,生活强加的条件(怀孕,出生,年龄,性别),结合大样本量,重复采样,并以家庭为基础的招聘将有助于揭示外周血细胞衍生的细胞因子模式,反映在体内调节有关Th 1/Th 2平衡和家族相关性。从图森婴儿免疫研究中的483个三人组中获得单核细胞:来自产前和产后的母亲,出生时和3个月时的婴儿,以及父亲。通过ELISA测定Con A/PMA刺激的上清液中的IFN-γ、IL-4、IL-13、IL-5和IL-10,并通过ELISA测定变应原刺激的上清液中的IFN-γ、IL-4和IL-13。有丝分裂原刺激的胎盘样本没有整体Th 2偏向,与产后不同的只是IFN-γ:IL-5比例适度降低。与父亲样品相比,母亲样品实际上产生较少的IL-10和IL-13,但产生较多的IL-5。新生儿也没有整体Th 2偏好,有丝分裂原刺激产生的IL-4、IL-5和IFN-γ比成人低约10倍,但IL-13和IL-10仅低2- 3倍。尽管存在这些组间差异,所有细胞因子均显示出显著的个体内正相关性(所有p < 0.001)。变应原刺激的结果与缺乏整体Th 2偏倚一致。有丝分裂原刺激揭示了亲子和父母-父母的相关性。因此,而不是一个全球性的Th 2的偏见,在怀孕的母亲和新生儿的细胞因子的生产似乎调节,以保持细胞因子之间的相对平衡,与母亲和婴儿的平衡的性质不同,并与生产的影响,包括共享的环境的家庭因素。
Regulation of human immune cell cytokine production in vivo is not well understood due in part to limitations on imposing experimental conditions. We proposed that life-imposed conditions (pregnancy, birth, age, gender), combined with large sample size, repeat sampling, and family-based recruitment would serve to reveal peripheral blood cell-derived cytokine patterns reflective of in vivo regulation regarding Th1/Th2 balance and familial correlation. Mononuclear cells were obtained from 483 trios in the Tucson Infant Immune Study: from mothers pre- and postpartum, infants at birth and at 3 mo, and fathers. Con A/PMA-stimulated supernatants were assayed by ELISA for IFN-γ, IL-4, IL-13, IL-5, and IL-10 and allergen-stimulated supernatants for IFN-γ, IL-4, and IL-13. Mitogen-stimulated prepartum samples were not globally Th2 biased, differing from postpartum only by a modestly reduced IFN-γ:IL-5 ratio. Prepartum samples actually produced less IL-10 and IL-13 although more IL-5 than paternal samples. Newborns were also not globally Th2 biased, with mitogen stimulation producing ~10-fold less IL-4, IL-5, and IFN-γ than adults but only 2- to 3-fold less IL-13 and IL-10. Despite these group differences, all cytokines showed marked positive intraindividual correlations (all p < 0.001). Allergen stimulation gave results consistent with a lack of global Th2 bias. Mitogen stimulation revealed parent-child and parent-parent correlations. Thus, rather than a global Th2 bias, cytokine production in pregnant mothers and newborns appears regulated so as to maintain a relative balance among the cytokines, with the nature of the balance differing in mothers and infants and with production influenced by familial factors that include shared environment.
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