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Postnatal Expansion, Maturation, and Functionality of MR1T Cells in Humans

Swarbrick, GM; Gela, A; Cansler, ME; Null, MD; Duncan, RB; Nemes, E; Shey, M; ... Lewinsohn, DA; + view all (2020) Postnatal Expansion, Maturation, and Functionality of MR1T Cells in Humans. Frontiers in Immunology , 11 , Article 556695. 10.3389/fimmu.2020.556695. Green open access

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Abstract

MR1-restricted T (MR1T) cells are defined by their recognition of metabolite antigens presented by the monomorphic MHC class 1-related molecule, MR1, the most highly conserved MHC class I related molecule in mammalian species. Mucosal-associated invariant T (MAIT) cells are the predominant subset of MR1T cells expressing an invariant TCR α-chain, TRAV1-2. These cells comprise a T cell subset that recognizes and mediates host immune responses to a broad array of microbial pathogens, including Mycobacterium tuberculosis. Here, we sought to characterize development of circulating human MR1T cells as defined by MR1-5-OP-RU tetramer labeling and of the TRAV1-2^{+} MAIT cells defined by expression of TRAV1-2 and high expression of CD26 and CD161 (TRAV1-2^{+}CD161^{++}CD26^{++} cells). We analyzed postnatal expansion, maturation, and functionality of peripheral blood MR1-5-OP-RU tetramer^{+} MR1T cells in cohorts from three different geographic settings with different tuberculosis (TB) vaccination practices, levels of exposure to and infection with M. tuberculosis. Early after birth, frequencies of MR1-5-OP-RU tetramer^{+} MR1T cells increased rapidly by several fold. This coincided with the transition from a predominantly CD4^{+} and TRAV1-2^{−} population in neonates, to a predominantly TRAV1-2^{+}CD161^{++}CD26^{++}CD8^{+} population. We also observed that tetramer^{+} MR1T cells that expressed TNF upon mycobacterial stimulation were very low in neonates, but increased ~10-fold in the first year of life. These functional MR1T cells in all age groups were MR1-5-OP-RU tetramer^{+}TRAV1-2^{+} and highly expressed CD161 and CD26, markers that appeared to signal phenotypic and functional maturation of this cell subset. This age-associated maturation was also marked by the loss of naïve T cell markers on tetramer^{+} TRAV1-2^{+} MR1T cells more rapidly than tetramer^{+}TRAV1-2^{−} MR1T cells and non-MR1T cells. These data suggest that neonates have infrequent populations of MR1T cells with diverse phenotypic attributes; and that exposure to the environment rapidly and preferentially expands the MR1-5-OP-RU tetramer^{+}TRAV1-2^{+} population of MR1T cells, which becomes the predominant population of functional MR1T cells early during childhood.

Type: Article
Title: Postnatal Expansion, Maturation, and Functionality of MR1T Cells in Humans
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fimmu.2020.556695
Publisher version: https://doi.org/10.3389/fimmu.2020.556695
Language: English
Additional information: © 2020 Swarbrick, Gela, Cansler, Null, Duncan, Nemes, Shey, Nsereko, Mayanja-Kizza, Kiguli, Koh, Hanekom, Hatherill, Lancioni, Lewinsohn, Scriba and Lewinsohn. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
Keywords: innate T cells, human mucosal immunology, MAIT cells, infant, tuberculosis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10113173
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