RESUMO
Low-level alloreactivity between mother and fetus may provide stimulation for fetal T helper type 1 (Th1) cell immune maturation. This study explored the effects of human leucocyte antigen (HLA) mismatch on materno-fetal interactions detected as cytokine responses and lymphoproliferation in mixed lymphocyte reactions, and whether this was altered in allergic women (n = 62) who have a Th2 propensity compared with non-allergic women (n = 65). HLA-DRbeta1 mismatch was associated with significantly increased Th1 interferon (IFN)-gamma, Th2 interleukin (IL)-13 and lymphoproliferative responses by both mothers and fetuses. Allergic women showed significantly lower IFN-gamma Th1 production in response to HLA-DRbeta1 mismatch. The infants of these women also showed significantly lower IL-10 and lower IFN-gamma production relative to IL-13. Both HLA-DRbeta1 mismatch and maternal allergy had significant independent effects on maternal IFN-gamma Th1 responses. Maternal allergy modifies HLA-mediated alloreactivity between the mother and the fetus, reducing Th1 activation. This may affect the cytokine milieu at the materno-fetal interface and could be implicated in the attenuated Th1 responses observed commonly in infants of atopic mothers.
Assuntos
Feto/imunologia , Antígenos HLA/imunologia , Hipersensibilidade/imunologia , Isoantígenos/imunologia , Células Th1/imunologia , Adolescente , Adulto , Proliferação de Células , Feminino , Número de Gestações/imunologia , Antígenos HLA/genética , Antígenos HLA-C/genética , Antígenos HLA-DR/genética , Antígenos HLA-DR/imunologia , Cadeias HLA-DRB1 , Teste de Histocompatibilidade , Humanos , Hipersensibilidade/genética , Interferon gama/metabolismo , Interleucina-10/metabolismo , Interleucina-13/metabolismo , Interleucina-6/metabolismo , Células Matadoras Naturais/imunologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Ativação Linfocitária/imunologia , Teste de Cultura Mista de Linfócitos , Gravidez , Linfócitos T/imunologia , Linfócitos T/metabolismo , Células Th1/metabolismo , Células Th2/imunologia , Células Th2/metabolismo , Adulto JovemRESUMO
BACKGROUND: During pregnancy, variations in maternal-foetal cellular interactions 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-gamma) IFN-gamma] 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-gamma/IL-13 and IFN-gamma/IL-10 responses were lower during pregnancy. Allergic mothers had lower IFN-gamma 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-gamma responses of allergic multigravid mothers were significantly lower than nonallergic 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 experienced by the foetus and will be further explored in the development of allergic disease during early life.
