Critical Role of Preconceptional Immunization for Protective and Nonpathological Specific Immunity in Murine Neonates

Uthoff, H.; Spenner, A.; Reckelkamm, Werner; Ahrens, Birgit; Wölk, G.; Hackler, Rolf; Hardung, Frank; Schaefer, Jürgen R.; Scheffold, Alexander; Renz, Harald; Herz, Udo

doi:10.4049/jimmunol.171.7.3485

Cited by 95 publications

(121 citation statements)

References 40 publications

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“…A large percentage of the OVA-sensitized groups developed skin hypersensitivity reactions consistent with a higher response to allergic stimuli (Herz et al, 2001). Similar findings were reported by Uthoff et al (2003), however in their study development of an IgE response against the same allergen was completely prevented early in life. This effect was mediated by diaplacental transfer of allergen-specific IgG 1 antibodies (Abs).…”

Section: Allergen Modelssupporting

confidence: 76%

“…The contradictory data may be explained by differences in the timing and mode of maternal exposure to allergens, and by considering evidence obtained by Uthoff et al (2003) and others that transplacental transfer of IgE but not IgG is minimal, and that transfer of allergen generally freely occurs. In a recent paper, Matson et al (2007) showed that the conditions surrounding allergy in the mother during gestation can influence the development of tolerance to that antigen later in life.…”

Section: Allergen Modelsmentioning

confidence: 99%

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Immunotoxicologic analysis of maternal transmission of asthma risk

Fedulov¹,

Kobzik²

2008

Journal of Immunotoxicology

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Section: Allergen Modelssupporting

confidence: 76%

Section: Allergen Modelsmentioning

confidence: 99%

Immunotoxicologic analysis of maternal transmission of asthma risk

Fedulov¹,

Kobzik²

2008

Journal of Immunotoxicology

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“…Interestingly, when high IgG1-antibody levels were found in the offspring, the generation of codfish-specific IgEantibodies was significantly suppressed. This phenomenon has already been observed previously (29,30). A possible explanation is that maternal IgG1 can function as blocking antibodies via formation of immune complexes, which then attach to the FcγRII-receptor and the B-cell receptor on B-cells, generating negative intracellular signals by crossaggregation of these receptors (30,31).…”

Section: Discussionmentioning

confidence: 78%

“…However, previous murine studies support our observations: There is a preventive effect of a specific sensitization of the mother against the respective antigen in the offspring via IgG-antibodies. At the same time, other factors transported from the mother may be responsible for a broad Th2-response toward multiple heterologous antigens in the newborns (28,30,31). The present study shows for the first time that the same effects can be achieved by the oral route when sucralfate is taken.…”

mentioning

confidence: 99%

Anti‐ulcer treatment during pregnancy induces food allergy in mouse mothers and a Th2‐bias in their offspring

Schöll¹,

Ackermann²,

Özdemir

et al. 2007

FASEB j.

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The treatment of dyspeptic disorders with anti-acids leads to an increased risk of sensitization against food allergens. As these drugs are taken by 30-50% of pregnant women due to reflux and heartburn, we aimed here to investigate the impact of maternal therapy with anti-acids on the immune response in the offspring in a murine model. Codfish extract as model allergen was fed with or without sucralfate, an anti-acid drug, to pregnant BALB/c mice during pregnancy and lactation. These mothers developed a codfish-specific allergic response shown as high IgG1 and IgE antibody levels and positive skin tests. In the next step we analyzed whether this maternal sensitization impacts a subsequent sensitization in the offspring. Indeed, in stimulated splenocytes of these offspring we found a relative Th2-dominance, because the Th1-and T-regulatory cytokines were significantly suppressed. Our data provide evidence that the anti-acid drug sucralfate supports sensitization against food in pregnant mice and favors a Th2-milieu in their offspring. From these results we propose that anti-acid treatment during pregnancy could be responsible for the increasing number of sensitizations against food allergens in young infants. Keywordssensitization against food; sucralfate; digestion; children; lactation The incidence of food allergies has been steadily increasing in the past decades and these allergies now affect ~3.5-4% of the adult population in the United States(1) and ~2.2-5.5% of children in the first year of life (2). Apart from several environmental influence factors, no genuine explanation accounts for this high number of children with food sensitization. It is known that the risk for sensitization in the offspring is higher when one or both parents, but especially when the mother is atopic (3). This may be due to hereditary factors, but an atopic mother may also transfer factors that directly bias the immune response of the infant to an allergic phenotype. For the adult population, we could show in previous studies that the risk to develop sensitization against food allergens increases with the usage of acid-suppressing drugs (4, 5), which are applied for the treatment of dyspeptic disorders such as gastric reflux, heartburn, and gastritis. We suggested that the hindered peptic digestion due to the elevated pH in the stomach leaves bigger fragments of alimentary proteins. These proteins could then elicit allergy due to persistence of their native conformation. © FASEBApproximately two-thirds of pregnant women suffer from heartburn and reflux due to low esophageal sphincter pressure, which is caused by changes of the hormone status (6). For their treatment, Richter suggested a step-up algorithm beginning with lifestyle modifications and dietary changes. As the first-line medical treatment antacids and sucralfate are used (7). The same review states that actually ~30-50% of women use antacids to relieve heartburn and other acid-reflux symptoms during pregnancy. For sucralfate, another nonabsorbable drug like antaci...

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“…This model thus excludes a critical role for transplacental passage of the allergen itself or allergen-specific immunoglobulins produced by the mother. 11,12 In fact, because treatment of asthmatic females with anti-IL-4 monoclonal antibodies before mating significantly ameliorated the offspring susceptibility to asthma, 9 our results point to a prominent role for maternal Th2 cytokines. Because T lymphocytes can provide the Th2 cytokines that both induce allergic inflammation and alter the lung function of asthmatics, 13 we postulated that allergen-specific T cells are sufficient, in our model, to mediate the maternal transfer of asthma risk.…”

mentioning

confidence: 75%

Adoptively Transferred Allergen-Specific T Cells Cause Maternal Transmission of Asthma Risk

Hubeau

Apostolou

Kobzik

2006

The American Journal of Pathology

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In addition to genetics and environment, maternal asthma is an identified risk factor for developing the disease during childhood. The mechanisms of this maternal effect remain poorly understood. We tested the role of allergen-specific T cells in the maternal transmission of asthma risk by modifying a model where offspring of asthmatic mothers are more prone to develop asthma after an intentionally suboptimal asthma induction. Normal BALB/c females were injected with allergen-specific T cells from ovalbumin-specific T cell receptor (TCR) transgenic DO11.10 donors before mating. Using the protocol of suboptimal asthma induction, offspring of normal and recipient mothers were tested for their susceptibility to develop asthma. Only pups of recipient mothers showed increased airway responsiveness (Penh), allergic airway inflammation with eosinophilia, and local Th2-skewed cytokine production. Although recipient mothers did not develop asthma, serum levels of interferon-␥, interleukin (IL)-4, IL-10, and IL-13 were significantly increased during pregnancy. Consistent with this finding, a subset of DO11.10 T cells persisted in the spleen and placenta of expectant recipient mothers. We conclude that allergen-specific T cells are sufficient to orchestrate the maternal transmission of asthma risk. Because overt maternal asthma was not required, our results suggest that similar maternal-fetal interactions may occur in other allergic disorders.

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Critical Role of Preconceptional Immunization for Protective and Nonpathological Specific Immunity in Murine Neonates

Cited by 95 publications

References 40 publications

Immunotoxicologic analysis of maternal transmission of asthma risk

Immunotoxicologic analysis of maternal transmission of asthma risk

Anti‐ulcer treatment during pregnancy induces food allergy in mouse mothers and a Th2‐bias in their offspring

Adoptively Transferred Allergen-Specific T Cells Cause Maternal Transmission of Asthma Risk

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