Dataset Information

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

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 ?-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.

SUBMITTER: Swarbrick GM

PROVIDER: S-EPMC7524872 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Swarbrick Gwendolyn M GM Gela Anele A Cansler Meghan E ME Null Megan D MD Duncan Rowan B RB Nemes Elisa E Shey Muki M Nsereko Mary M Mayanja-Kizza Harriet H Kiguli Sarah S Koh Jeffrey J Hanekom Willem A WA Hatherill Mark M Lancioni Christina C Lewinsohn David M DM Scriba Thomas J TJ Lewinsohn Deborah A DA

Frontiers in immunology 20200916

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 <i> ...[more]

PMID: 33042140

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Project description:BACKGROUND:Cumulus cells (CC) encapsulate growing oocytes and support their growth and development. Transcriptomic signatures of CC have the potential to serve as valuable non-invasive biomarkers for oocyte competency and potential. The present sibling cumulus-oocyte-complex (COC) cohort study aimed at defining functional variations between oocytes of different maturity exposed to the same stimulation conditions, by assessing the transcriptomic signatures of their corresponding CC. CC were collected from 18 patients with both germinal vesicle and metaphase II oocytes from the same cycle to keep the biological variability between samples to a minimum. RNA sequencing, differential expression, pathway analysis, and leading-edge were performed to highlight functional differences between CC encapsulating oocytes of different maturity. RESULTS:Transcriptomic signatures representing CC encapsulating oocytes of different maturity clustered separately on principal component analysis with 1818 genes differentially expressed. CCs encapsulating mature oocytes were more transcriptionally synchronized when compared with CCs encapsulating immature oocytes. Moreover, the transcriptional activity was lower, albeit not absent, in CC encapsulating mature oocytes, with 2407 fewer transcripts detected than in CC encapsulating immature (germinal vesicle - GV) oocytes. Hallmark pathways and ovarian processes that were affected by oocyte maturity included cell cycle regulation, steroid metabolism, apoptosis, extracellular matrix remodeling, and inflammation. CONCLUSIONS:Herein we review our findings and discuss how they align with previous literature addressing transcriptomic signatures of oocyte maturation. Our findings support the available literature and enhance it with several genes and pathways, which have not been previously implicated in promoting human oocyte maturation. This study lays the ground for future functional studies that can enhance our understanding of human oocyte maturation.

Dataset Information

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

Publications

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

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