Acquisition of innate-like microbial reactivity in mucosal tissues during human fetal MAIT-cell development

TLDR

MAIT cells are a large, evolutionarily conserved, MR1‑restricted T‑cell subset that is rare and immature in fetal thymus, spleen, and mesenteric lymph nodes, but their development before birth may help protect newborns from pathogens, although the mechanisms remain poorly understood. The study investigates the development of MAIT cells in second‑trimester human fetal tissues and shows that, unlike in mice, commensal microflora is not required for their maturation. Mature IL‑18Rα⁺ CD8αα MAIT cells are enriched in fetal small intestine, liver, and lung, express CD127 and Ki67, proliferate to E.

Abstract

Innate-like, evolutionarily conserved MR1-restricted mucosa-associated invariant T (MAIT) cells represent a large antimicrobial T-cell subset in humans. Here, we investigate the development of these cells in second trimester human fetal tissues. MAIT cells are rare and immature in the fetal thymus, spleen and mesenteric lymph nodes. In contrast, mature IL-18Rα+ CD8αα MAIT cells are enriched in the fetal small intestine, liver and lung. Independently of localization, MAIT cells express CD127 and Ki67 in vivo and readily proliferate in response to Escherichia coli in vitro. Maturation is accompanied by the gradual post-thymic acquisition of the PLZF transcription factor and the ability to produce IFNγ and IL-22 in response to bacteria in mucosa. Thus, MAIT cells acquire innate-like antimicrobial responsiveness in mucosa before exposure to environmental microbes and the commensal microflora. Establishment of this arm of immunity before birth may help protect the newborn from a range of pathogenic microbes. Mucosa-associated invariant T (MAIT) cells are a recently described subset of unconventional, innate-like T cells and their development is not well understood. Here, the authors analyse MAIT cells in fetal human tissues and show that, unlike in mice, the commensal microflora is not necessary for their maturation in humans.