Original article Pregnancy IFN-c responses to foetal alloantigens are altered by maternal allergy and gravidity status Patterns of perinatal immune responses have been con- vincingly linked to the risk of subsequent allergic disease. The most consistent of these observations has been that the ÔnormalÕ T-helper cell type 1 (Th-1) immaturity of the neonatal period is more profound in newborns with allergic predisposition (1–5). This has generated enor- mous interest in the potential factors that could influence early immune function and predisposition to disease. An increasing number of studies have examined the effects of environmental influences during pregnancy and demon- strated that exogenous factors, such as microbial expo- sure (6), maternal diet (7, 8) and smoking (9) can have effects on developing immune responses. However, endogenous influences such as variations in cellular interactions at the maternal–foetal interface have not been extensively studied. Immune interactions between mother and foetus play an important role in determining cytokine homeostasis during pregnancy. Successful pregnancy involves a rela- tive Th-2 cytokine bias in the placenta, which occurs under the influence of hormonal changes (10–12). This is reflected by foetal responses at birth which are also relatively ÔTh-2 skewedÕ (4), indicating that this shift in cytokine expression has a critical effect on subsequent immune development. Direct interaction between mother and foetus has the capacity to influence the pattern of foetal immune development by subtle alterations of immune responses during pregnancy. A recent exploratory study by our group showed that maternal responses to foetal alloan- tigen were directly related to foetal Th-2 [interleukin-13 (IL-13), IL-10] cytokine responses and allergic outcomes at 6 years of age (13). Here, we explore the hypothesis that allergic mothers, who have a predisposition towards Th-2-like responses to allergens, also produce such a Background: During pregnancy, variations in maternal–foetal cellular interac- tions may influence immune programming. This study was carried out to determine if maternal responses to foetal alloantigens are altered by maternal allergic disease and/or previous pregnancies. Methods: For this cohort study, peripheral blood was collected from allergic (n = 69) and nonallergic (n = 63) pregnant women at 20, 30, 36-week gestation and 6-week postpartum (pp). Cord blood was collected at delivery. Mixed lymphocyte reactions were used to measure maternal cytokine responses [interleukin-6 (IL-6), IL-10, IL-13 and (interferon-c) IFN-c] at each time point towards foetal mononuclear cells. Results: Maternal cytokine responses during pregnancy (20, 30 and 36 weeks) were suppressed compared to the responses at 6-week pp. The ratio of maternal IFN-c/IL-13 and IFN-c/IL-10 responses were lower during pregnancy. Allergic mothers had lower IFN-c responses at each time-point during pregnancy with the greatest difference in responses observed at 36-week gestation. When allergic and nonallergic women were further stratified by gravidity group, IFN-c responses of allergic multigravid mothers were significantly lower than nonal- lergic multigravid mothers during pregnancy. Conclusions: During normal pregnancy, peripheral T-cell cytokine responses to foetal alloantigens may be altered by both allergic status of the mother and previous pregnancies. These factors could influence the cytokine milieu experi- enced by the foetus and will be further explored in the development of allergic disease during early life. L. A. Breckler 1 , J. Hale 1 , A. Taylor 1 , J. A. Dunstan 1 , C. A. Thornton 2 , S. L. Prescott 1 1 School of Paediatrics and Child Health, University of Western Australia, Perth, WA, Australia, 2 Institute of Life Science, School of Medicine, Swansea University, Swansea, UK Key words: allergy; alloimmune response; maternal– foetal interaction; pregnancy; T helper. Susan L. Prescott School of Paediatrics and Child Health University of Western Australia PO Box D184 Princess Margaret Hospital Perth WA 6001 Australia Accepted for publication 20 February 2008 Abbreviations: 2ME, 2-mercaptoethanol; CB, cord blood; HLA, human leukocyte antigen; IFN, interferon; IL, interleukin; MLR, mixed lymphocyte reaction; MNC, mononuclear cells; pp, post- partum; RPMI, Roswell Park Memorial Institute; SPT, skin prick test; Th, T helper; T Reg , regulatory T cells; URD, unrelated donor. Allergy 2008: 63: 1473–1480 Ó 2008 The Authors Journal compilation Ó 2008 Blackwell Munksgaard DOI: 10.1111/j.1398-9995.2008.01718.x 1473