Active suppression of intestinal CD4(+)TCRαβ(+) T-lymphocyte maturation during the postnatal period

Nat Commun. 2015 Jul 21:6:7725. doi: 10.1038/ncomms8725.

Abstract

Priming of the mucosal immune system during the postnatal period substantially influences host-microbial interaction and susceptibility to immune-mediated diseases in adult life. The underlying mechanisms are ill defined. Here we show that shortly after birth, CD4 T cells populate preformed lymphoid structures in the small intestine and quickly acquire a distinct transcriptional profile. T-cell recruitment is independent of microbial colonization and innate or adaptive immune stimulation but requires β7 integrin expression. Surprisingly, neonatal CD4 T cells remain immature throughout the postnatal period under homeostatic conditions but undergo maturation and gain effector function on barrier disruption. Maternal SIgA and regulatory T cells act in concert to prevent immune stimulation and maintain the immature phenotype of CD4 T cells in the postnatal intestine during homeostasis. Active suppression of CD4 T-cell maturation during the postnatal period might contribute to prevent auto-reactivity, sustain a broad TCR repertoire and establish life-long immune homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • CD4-Positive T-Lymphocytes / physiology*
  • Growth and Development / immunology*
  • Immunity, Mucosal*
  • Immunophenotyping
  • Intestines / immunology*
  • Intestines / microbiology
  • Mice, Transgenic