title: Delayed maturation of an IL-12-producing dendritic cell subset explains the early Th2 bias in neonatal immunity.
abstract: Primary neonatal T cell responses comprise both T helper (Th) cell subsets, but Th1 cells express high levels of interleukin 13 receptor alpha1 (IL-13R alpha 1), which heterodimerizes with IL-4R alpha. During secondary antigen challenge, Th2-produced IL-4 triggers the apoptosis of Th1 cells via IL-4R alpha/IL-13R alpha 1, thus explaining the Th2 bias in neonates. We show that neonates acquire the ability to overcome the Th2 bias and generate Th1 responses starting 6 d after birth. This transition was caused by the developmental maturation of CD8 alpha(+)CD4(-) dendritic cells (DCs), which were minimal in number during the first few days of birth and produced low levels of IL-12. This lack of IL-12 sustained the expression of IL-13R alpha 1 on Th1 cells. By day 6 after birth, however, a significant number of CD8 alpha(+)CD4(-) DCs accumulated in the spleen and produced IL-12, which triggered the down-regulation of IL-13R alpha 1 expression on Th1 cells, thus protecting them against IL-4-driven apoptosis.
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO 65212, USA.
authors.forename: Hyun-Hee
authors.initials: HH
authors.lastname: Lee
authors.forename: Christine M
authors.initials: CM
authors.lastname: Hoeman
authors.forename: John C
authors.initials: JC
authors.lastname: Hardaway
authors.forename: F Betul
authors.initials: FB
authors.lastname: Guloglu
authors.forename: Jason S
authors.initials: JS
authors.lastname: Ellis
authors.forename: Renu
authors.initials: R
authors.lastname: Jain
authors.forename: Rohit
authors.initials: R
authors.lastname: Divekar
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Tartar
authors.forename: Cara L
authors.initials: CL
authors.lastname: Haymaker
authors.forename: Habib
authors.initials: H
authors.lastname: Zaghouani