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

Priming of the mucosal immune system during the early postnatal period substantially influences the host-microbial interaction and susceptibility to immune-mediated diseases in adult life. The underlying mechanisms, however, are ill defined. Here, we investigated the migratory routes, immune function, and maturation kinetic of intestinal mucosal CD4 T lymphocytes during the postnatal period. Shortly after birth, CD4 T cells populate preformed lymphoid structures and quickly acquire a distinct transcriptional profile. T cell recruitment is independent of microbial colonization, innate immune receptor or T cell receptor (TCR)-mediated stimulation but requires β7 integrin expression. Surprisingly, neonatal CD4 T cells remain immature throughout the postnatal period, despite exposure to the rapidly evolving enteric microbiota. Yet, they are able to readily undergo maturation and gain effector function upon barrier disruption by invasive infection with rotavirus or Salmonella enterica as well as upon adoptive transfer into adult recipients. Maternal SIgA and signals intrinsic to Peyer’s patches act to prevent immune stimulation and maintain the immature phenotype of CD4 T cells in the postnatal intestine. Our results identify mechanisms that actively suppress CD4 cell maturation during the postnatal period, and that might significantly contribute to prevent auto-reactivity, sustain a broad TCR repertoire and establish life-long immune homeostasis.