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Fetal peripheral blood mononuclear cell proliferative responses to mitogenic and allergenic stimuli during gestation
A C Jones1, E A Miles, J O Warner
1Department of Child Health, University of Southampton, England.
Insights
The fetal immune system can respond to common allergens around 22 weeks gestation. In utero allergen exposure may lead to primary sensitization and positive immune responses at birth.
Area of Science:
- Immunology
- Developmental Biology
- Allergy Research
Background:
- The development of fetal immune responses to allergens is not fully understood.
- Investigating immune system maturation in premature infants is crucial for understanding early-life allergy development.
Purpose of the Study:
- To determine the gestational age at which the fetal immune system mounts a proliferative response to common allergens.
- To explore the impact of in utero allergen exposure on fetal immune sensitization.
Main Methods:
- Peripheral blood mononuclear cells (PBMC) from fetuses and premature infants (15-34 weeks gestation) were stimulated with mitogens and allergens.
- Proliferative responses were measured by 3H thymidine incorporation and expressed as ratios and percent positive responders.
- Maternal exposure to birch pollen was assessed in relation to infant immune responses.
Main Results:
- Fetal immune cell proliferation increased with gestational age for phytohaemagglutinin (PHA) and several allergens (cat fur, birch pollen, beta-lactoglobulin).
- Significant allergen-specific responses were observed around 22 weeks gestation, with higher responses in infants >22 weeks.
- Infants born to mothers exposed to birch pollen beyond 22 weeks gestation showed enhanced responses to birch pollen.
Conclusions:
- The fetal immune system demonstrates responsiveness to common allergens starting around 22 weeks gestation.
- In utero exposure to allergens from approximately 22 weeks gestation may lead to primary sensitization and subsequent positive immune responses at birth.
Abstract:
Blood samples were obtained from fetuses and premature babies (n = 51) (15-34 weeks gestation) to determine at what stage the fetal immune system was able to produce a positive proliferative response to common allergens. Peripheral blood mononuclear cells (PBMC) were stimulated with the mitogen, phytohaemagglutinin (PHA), and the allergens, house dust mite, cat fur, birch tree pollen, beta-lactoglobulin, ovalbumin and bee venom (mellitin). Results were expressed as ratios of stimulated to unstimulated 3H thymidine incorporation, and as percent positive responders. There was an increase in proliferation ratio which correlated with increasing gestational age for PHA (p < 0.0001), cat fur (p = 0.042), birch pollen (p = 0.022) and beta-lactoglobulin (p = 0.006). The point in gestation when cells from some individuals began responding to the allergens with a ratio of 2.0 was at approximately 22 weeks. PBMC proliferative response ratios were higher from samples from babies > 22 weeks gestation compared to < 22 weeks for the mitogen and all allergens, except mellitin. There was also a greater proportion of positive responders from samples > 22 weeks compared to < 22 weeks for the mitogen and all allergens, except mellitin. Maternal exposure to birch pollen, which has a discrete season, was assessed to determine whether exposure had occurred at 22 weeks gestation or beyond. Results showed a higher proliferative response in infant cells stimulated with birch pollen (p = 0.005) and higher proportion of positive responders (p = 0.01) in the group of babies whose mothers had been exposed to birch pollen beyond 22 weeks, compared to those whose mothers had not been so exposed. These results suggest that in utero fetal exposure to an allergen from around 22 weeks gestation may result in primary sensitisation to that allergen, leading to positive proliferative responses, at birth.