title: Transplacental priming of the human immune system to environmental allergens: universal skewing of initial T cell responses toward the Th2 cytokine profile.
abstract: The expression of Th2-skewed immunity against soluble protein Ags present in the normal environment is recognized as the primary cause of allergic inflammation in atopics. In contrast, nonallergic normal individuals display low level Th1-skewed immunity against the same Ags ("allergens"), which is perceived as conferring protection against Th2-dependent allergic sensitization. The type of T cell memory that develops against these Ags is currently believed to be the result of complex interactions between environmental and genetic susceptibility factors, which occur postnatally when the naive immune system directly confronts the outside environment. The results of the present study challenge this general concept. We demonstrate here for the first time that Th2-skewed responses to common environmental allergens, comprising IL-4, IL-5, IL-6, IL-9, and IL-13, are present in virtually all newborn infants and are dominated by high level production of IL-10. Moreover, these responses are demonstrable within 24 h of culture initiation, arguing against a significant contribution from covert in vitro T cell priming and/or differentiation. These findings imply that the key etiologic factor in atopic disease may not be the initial acquisition of allergen-specific Th2-skewed immunity per se, but instead may be the efficiency of immune deviation mechanisms, which in normal (nonatopic) individuals redirect these fetal immune responses toward the Th1 cytokine phenotype.
authors.affiliation: Division of Cell Biology, TVW Telethon Institute for Child Health Research, Perth, Western Australia, Australia.
authors.forename: S L
authors.initials: SL
authors.lastname: Prescott
authors.forename: C
authors.initials: C
authors.lastname: Macaubas
authors.forename: B J
authors.initials: BJ
authors.lastname: Holt
authors.forename: T B
authors.initials: TB
authors.lastname: Smallacombe
authors.forename: R
authors.initials: R
authors.lastname: Loh
authors.forename: P D
authors.initials: PD
authors.lastname: Sly
authors.forename: P G
authors.initials: PG
authors.lastname: Holt
mesh_terms: D000485:Allergens / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D005333:Fetus / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000485:Allergens; D016207:Cytokines