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

Reinhold Förster,Mathias W Hornef,Siegfried Weiss,Jenny Freitag,Olga Schulz,Marijana Basic,Anne Brennecke,Kasra Hassani,Oliver Pabst,Matthias Lochner,Kai Yu,Norbert Wagner,Natalia Torow,André Bleich,Tim Sparwasser

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.

Highlights

Priming of the mucosal immune system during the postnatal period substantially influences host–microbial interaction and susceptibility to immune-mediated diseases in adult life
Immune cell subset analysis revealed that myeloid cells (macrophages, dendritic cells (DCs) and eosinophils) and gd T lymphocytes were present at birth and their numbers remained stable during postnatal development (Fig. 1b)
This increase was mainly due to the strong expansion of CD8ab þ TCRab þ T lymphocytes, which accounted for the majority of TCRab þ cells in the adult animal, but was supported by the emergence of CD8aa þ TCRab þ and CD4 þ CD8aa þ TCRab þ T cells (Fig. 1c,d)

Summary

Introduction

Priming of the mucosal immune system during the postnatal period substantially influences host–microbial interaction and susceptibility to immune-mediated diseases in adult life. In animal models, microbial immune stimulation during early development has been shown to influence immune cell recruitment and function as well as the susceptibility to allergic and autoimmune disease[13,14,15,16,17,18]. These findings have led to the definition of a ‘window of opportunity’ during the early postnatal development, with life-long consequences for the host’s immune system. These mechanisms might contribute to restrict the emergence of cross-reactive immune cells and sustain a broad TCR repertoire throughout infancy

Methods

Results

Conclusion