Postnatal Expansion, Maturation, and Functionality of MR1T Cells in Humans
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Date
2020
Journal Title
Journal ISSN
Volume Title
Publisher
Frontiers in Immunology
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 a-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.
Description
Keywords
Innate T cells, Human mucosal immunology, MAIT cells, Infant, Tuberculosis
Citation
Swarbrick GM, Gela A, Cansler ME, Null MD, Duncan RB, Nemes E, Shey M, Nsereko M, Mayanja-Kizza H, Kiguli S, Koh J, Hanekom WA, Hatherill M, Lancioni C, Lewinsohn DM, Scriba TJ and Lewinsohn DA (2020) Postnatal Expansion, Maturation, and Functionality of MR1T Cells in Humans. Front. Immunol. 11:556695. doi: 10.3389/fimmu.2020.556695