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

Gwendolyn M. Swarbrick, Anele Gela, Meghan E. Cansler, Megan D. Null, Rowan B. Duncan, Elisa Nemes, Muki Shey, Mary Nsereko, Harriet Mayanja-Kizza, Sarah Kiguli, Jeffrey Koh, Willem A. Hanekom, Mark Hatherill, Christina Lancioni, David M. Lewinsohn, Thomas J. Scriba, Deborah A. Lewinsohn

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number556695
JournalFrontiers in immunology
Volume11
DOIs
StatePublished - Sep 16 2020

Keywords

  • MAIT cells
  • human mucosal immunology
  • infant
  • innate T cells
  • tuberculosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Postnatal Expansion, Maturation, and Functionality of MR1T Cells in Humans'. Together they form a unique fingerprint.

Cite this