Fetal Cord Blood: Aspects of Heightened Immune Responses

Schaub, Bianca; Tantisira, Kelan G.; Gibbons, Fiona K.; He, Hong; Litonjua, Augusto A.; Gillman, Matthew W.; Weiss, Scott T.; Perkins, David L.; Gold, Diane R.

doi:10.1007/s10875-005-4180-5

Cited by 24 publications

(26 citation statements)

References 52 publications

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“…An example of a feedback mechanism of cytokine regulation involving induction of IL-10 by all cytokines that utilize the common γ-chain as a component of their receptors has been described previously (23) and whether a mechanism similar to this but expanded in scope might be responsible is one such possibility. That these close direct relations among the cytokines produced are not unique to stimulation with Con A/PMA is shown by Hartel et al (24), who reported a similar close direct relation between IL-10 and IL-4 following stimulation with PMA/ionomycin, by Gabrielsson et al (25), who showed a direct relation between the percentage of cells producing IL-4 and IFN-γ in cord blood stimulated with PHA, and by Schaub et al (26), who found a significant relation between IL-13 production and the proliferation response to PHA. The precise mechanisms responsible for these correlations remain to be elucidated.…”

Section: Discussionmentioning

confidence: 53%

Th1/Th2 Patterns and Balance in Cytokine Production in the Parents and Infants of a Large Birth Cohort

Halonen

Lohman

Stern

et al. 2009

The Journal of Immunology

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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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Section: Discussionmentioning

confidence: 53%

Th1/Th2 Patterns and Balance in Cytokine Production in the Parents and Infants of a Large Birth Cohort

Halonen

Lohman

Stern

et al. 2009

The Journal of Immunology

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“…These studies propose that positive correlation between maternal and fetal immunoglobulin levels is related to the quantity and nature of allergens present in the family environment. Indeed, it is believed that several allergens may be transferred through the placenta or in amniotic fluid, thus gaining access to gut-associated lymphoid tissue 10, 42, 43. This hypothesis is supported by the detection of antigen presenting cells in the placenta during pregnancy and the detection of Der p 1 in amniotic fluid and cord blood 10…”

Section: Discussionmentioning

confidence: 98%

Relationships among prenatal aeroallergen exposure and maternal and cord blood IgE: Project ACCESS

Peters¹,

Suglia²,

Platts-Mills³

et al. 2009

Journal of Allergy and Clinical Immunology

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Background While some evidence suggests that antigen sensitization may begin prenatally, the influence of maternal allergen exposure during pregnancy has not been fully elucidated. Objectives We examined the relationship between prenatal maternal aeroallergen exposure and cord blood total immunoglobulin E (IgE) and the potential mediating/indirect effect of maternal immune response. Methods This study was performed in 301 mother-infant pairs enrolled in the Asthma Coalition on Community, Environment, and Social Stress (ACCESS) project, a study examining the effects of prenatal and early life social and physical environmental exposures on urban asthma risk. Dust samples collected prenatally from mothers’ bedrooms were analyzed for cockroach and dust mite allergens. Cord blood was analyzed for total IgE and maternal serum collected during pregnancy for total and specific IgE. We assessed the relationship between prenatal exposure and cord blood total IgE and the potential mediation effect adjusting for maternal age, race, education, smoking status and dust collection season; and child’s gender and season of birth. Results In multivariate models, elevated prenatal dust mite levels (> 0.2 µg/g) increased cord blood IgE concentrations by 29% (p=0.08) and continuous dust mite concentration was associated with a significant non-linear increase in cord blood IgE (p=0.02). Elevated prenatal exposure to cockroach allergen (> 2 U/g) was not associated with cord blood IgE, but showed a significant indirect relationship through maternal total IgE (β=0.23; 95% CI: 0.08, 0.41). Conclusions These results demonstrate that maternal prenatal exposure to household allergens may impact cord blood IgE albeit the underlying mechanism may be allergen-specific. Clinical Implications Maternal prenatal inhalant allergen exposure may precipitate infant immune response although the pathway of the effect may differ by allergen. Capsule Summary Prenatal exposure to dust mite was associated with increased cord blood total IgE whereas the relationship between prenatal cockroach exposure and total cord blood IgE was only observed through the indirect effect of maternal allergic response.

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“…Many authors have already dealt with cytokines in cord blood in relation to allergy but they focused mainly on IFN-, IL-4 and IL-13 (Chung et al 2007;Schaub et al 2005;Silberer et al 2008) though many different cytokines are involved in allergy development and other ones have anti-allergic effect. The cytokines tested by us are supposed to have some relationship to the induction and regulation of allergic reaction: T H 1 (IL-2, IFN-) and T H 2 (IL-4, IL-13) cytokines which inhibit or support allergy development, respectively (Chung et al 2007), IL-10 and TGF- promoting isotype switch towards IgA (Fayette et al 1997) which is believed to act against allergy development; IL-4 and IL-13 being important for IgE production (Fayette et al 2007;Graves et al 2000;Tanaka et al 2001); IL-10 and TGF- mediating the establishment of peripheral tolerance hampering the rise of allergy (Jutel et al 2003); EGF and TGF- as growth and differentiation factors of great importance for intestine maturation (McGee et al 1992;Nair et al 2008), the failure of which can cause increased intestinal permeability leading to easier access of allergens to the immune system resulting in allergy induction; IL-1, IL-8 and TNF- act as inflammatory cytokines (Mohammed et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Cytokine expression in cord blood cells of children of healthy and allergic mothers

et al. 2010

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To determine some early signs connected with the increased risk of future allergy development, gene expression and production of selected cytokines were tested in children of allergic mothers and compared with newborns of healthy mothers. Expression of IL-1β, IL-2, IL-4, IL-8, IL-10, IL-13, IFN-γ, TNF-α, TGF-β and EGF was tested in cord blood cells using real-time PCR and production of these cytokines was evaluated in cord sera by ELISA. Gene expression of IL-2, IL-4, IL-8, IFN-γ, IL-1β, TNF-α and TGF-β was decreased and that of IL-10, IL-13 and EGF increased in children of allergic mothers in comparison with those of healthy mothers. Significant differences in sera of healthy and allergic groups were only in IL-10 and EGF. Different relationship among serum cytokine levels reflects the fact that the cytokines are not produced only by blood cells. Significantly decreased production of EGF in newborns of allergic mothers could negatively influence maturation of mucosal membranes of these children and support thus their easier allergization. Allergic phenotype pointing to the bias to T(H)2 response and to possibly impaired intestine maturation was apparent already on the level of cord blood and could serve as a predictive sign of increased allergy risk.

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Fetal Cord Blood: Aspects of Heightened Immune Responses

Cited by 24 publications

References 52 publications

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

Relationships among prenatal aeroallergen exposure and maternal and cord blood IgE: Project ACCESS

Cytokine expression in cord blood cells of children of healthy and allergic mothers

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