Delayed maturation of an IL-12-producing dendritic cell subset explains the early Th2 bias in neonatal immunity

J Exp Med. 2008 Sep 29;205(10):2269-80. doi: 10.1084/jem.20071371. Epub 2008 Sep 1.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Animals, Newborn / immunology*
  • Apoptosis / immunology
  • Cell Survival
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Immunity / immunology*
  • Interferon-gamma / immunology
  • Interleukin-12 / biosynthesis*
  • Interleukin-12 / immunology
  • Interleukin-13 Receptor alpha1 Subunit / genetics
  • Interleukin-13 Receptor alpha1 Subunit / immunology
  • Interleukin-4 / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Rabbits
  • Rats
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • Th1 Cells / immunology
  • Th2 Cells / cytology
  • Th2 Cells / immunology*

Substances

  • Interleukin-13 Receptor alpha1 Subunit
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma