Allergic women show reduced T helper type 1 alloresponses to fetal human leucocyte antigen mismatch during pregnancy

• Published in: Clinical and experimental immunology Vol. 159; no. 1; pp. 65 - 72
• Main Authors: Prescott, S.L, Breckler, L.A, Witt, C.S, Smith, L, Dunstan, J.A, Christiansen, F.T
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.01.2010; Blackwell Publishing Ltd; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Adolescent; Adult; allergic disease; allergy; Analytical, structural and metabolic biochemistry; Antigens; Biological and medical sciences; Cell Proliferation; cord blood; Cytokines; Female; Fetus - immunology; Fetuses; Fundamental and applied biological sciences. Psychology; Gravidity - immunology; Histocompatibility Testing; HLA Antigens - genetics; HLA Antigens - immunology; HLA typing; HLA-C; HLA-C Antigens - genetics; HLA-DR Antigens - genetics; HLA-DR Antigens - immunology; HLA-DRB1 Chains; HLA-DRβ1; Humans; hypersensitivity; Hypersensitivity - genetics; Hypersensitivity - immunology; Interferon-gamma - metabolism; Interleukin-10 - metabolism; Interleukin-13 - metabolism; Interleukin-6 - metabolism; Isoantigens - immunology; Killer Cells, Natural - immunology; Leukocytes; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Lymphocyte Activation - immunology; Lymphocyte Culture Test, Mixed; MLR; Pregnancy; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Th1 Cells - immunology; Th1 Cells - metabolism; Th2 Cells - immunology; Th2 Cells - metabolism; Translational Studies; Young Adult; Allergy; HLA-System; cord blood; Major histocompatibility system; HLA typing; Th1 lymphocyte; Biochemistry; Blood; MLR; Adult; Female; Fetus; cytokines; Woman; allergic disease; Class I histocompatibility antigen; Human; Incompatibility; Immunopathology; Typing; Cytokine; HLA-C-Locus; HLA-C; HLA-DRβ1; Pregnancy; Umbilical cord
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2009.04042.x

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-DRβ1 mismatch was associated with significantly increased Th1 interferon (IFN)-γ, Th2 interleukin (IL)-13 and lymphoproliferative responses by both mothers and fetuses. Allergic women showed significantly lower IFN-γ Th1 production in response to HLA-DRβ1 mismatch. The infants of these women also showed significantly lower IL-10 and lower IFN-γ production relative to IL-13. Both HLA-DRβ1 mismatch and maternal allergy had significant independent effects on maternal IFN-γ 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.