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

Natalia Torow, Kai Yu, Kasra Hassani, Jenny Freitag, Olga Schulz, Marijana Basic, Anne Brennecke, Tim Sparwasser, Norbert Wagner, André Bleich, Matthias Lochner, Siegfried Weiss, Reinhold Förster, Oliver Pabst and Mathias W. Hornef ()
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Natalia Torow: Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School
Kai Yu: Institute of Immunology, Hannover Medical School, Hannover
Kasra Hassani: Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School
Jenny Freitag: Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School, Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI)
Olga Schulz: Institute of Immunology, Hannover Medical School, Hannover
Marijana Basic: Institute for Laboratory Animal Science, Hannover Medical School, Hannover
Anne Brennecke: Helmholtz Centre for Infection Research
Tim Sparwasser: Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School, Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI)
Norbert Wagner: RWTH Aachen University Hospital
André Bleich: Institute for Laboratory Animal Science, Hannover Medical School, Hannover
Matthias Lochner: Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School, Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI)
Siegfried Weiss: Helmholtz Centre for Infection Research
Reinhold Förster: Institute of Immunology, Hannover Medical School, Hannover
Oliver Pabst: Institute of Immunology, Hannover Medical School, Hannover
Mathias W. Hornef: Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms8725

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