A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage

Hui-Fern Koay; Nicholas A Gherardin; Anselm Enders; Liyen Loh; Laura K Mackay; Catarina F Almeida; Brendan E Russ; Claudia A Nold-Petry; Marcel F Nold; Sammy Bedoui; Zhenjun Chen; Alexandra J Corbett; Sidonia BG Eckle; Bronwyn Meehan; Yves d'Udekem; Igor E Konstantinov; Martha Lappas; Ligong Liu; Chris C Goodnow; David P Fairlie; Jamie Rossjohn; Mark M Chong; Katherine Kedzierska; Stuart P Berzins; Gabrielle T Belz; James McCluskey; Adam P Uldrich; Dale I Godfrey; Daniel G Pellicci

Journal article

A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage

Hui-Fern Koay, Nicholas A Gherardin, Anselm Enders, Liyen Loh, Laura K Mackay, Catarina F Almeida, Brendan E Russ, Claudia A Nold-Petry, Marcel F Nold, Sammy Bedoui, Zhenjun Chen, Alexandra J Corbett, Sidonia BG Eckle, Bronwyn Meehan, Yves d'Udekem, Igor E Konstantinov, Martha Lappas, Ligong Liu, Chris C Goodnow, David P Fairlie Show all

NATURE IMMUNOLOGY | NATURE PUBLISHING GROUP | Published : 2016

DOI: 10.1038/ni.3565

Abstract

Mucosal-associated invariant T cells (MAIT cells) detect microbial vitamin B2 derivatives presented by the antigen-presenting molecule MR1. Here we defined three developmental stages and checkpoints for the MAIT cell lineage in humans and mice. Stage 1 and stage 2 MAIT cells predominated in thymus, while stage 3 cells progressively increased in abundance extrathymically. Transition through each checkpoint was regulated by MR1, whereas the final checkpoint that generated mature functional MAIT cells was controlled by multiple factors, including the transcription factor PLZF and microbial colonization. Furthermore, stage 3 MAIT cell populations were expanded in mice deficient in the antigen-pr..

View full abstract

University of Melbourne Researchers

Dale Godfrey Author Microbiology and Immunology

Alexandra Corbett Author Microbiology and Immunology

Igor Konstantinov Author Paediatrics Royal Children's Hospital

Gabrielle Belz Author Medical Biology (w.e.h.i.)

Related Projects (2)

MAIT CELL DEVELOPMENT

This project will investigate the factors that regulate the development and maintenance of a recently identified population of white blood c..

IMMUNE REGULATION EFFECTOR FUNCTION AND THERAPY

We seek to understand how white blood cells detect and destroy disease, and how molecules of the immune system punch holes in diseased cells..

Grants

Awarded by National Health and Medical Research Council of Australia

Awarded by Australian Research Council

Funding Acknowledgements

We thank the staff of the University of Melbourne DMI and MBC flow cytometry facilities and M. Camilleri, D. Taylor and animal house staff for animal husbandry and assistance with genotyping; J.C. Zuniga-Pflucker (University of Toronto) for OP9 and OP9-DL1 cells; T. Hansen (Washington University School of Medicine) for the MR1-blocking antibody 8F2.F9; and the clinical research midwives G. Christophers, G. Pell and R. Murdoch and the Obstetrics and Midwifery staffs of the Mercy Hospital for Women for assistance with collection of the cord blood samples. Supported by the National Health and Medical Research Council of Australia (1083942, 1013667 and 1016629; CDF 1035858 to A.E.; ECF 1054431 to D.G.P.; Senior Principal Research Fellowships 1020770 and 1027369 to D.I.G. and D.P.F.; Australia Fellowship AF50 to J.R.; CDF2 Fellowship 1047025 to M.C.; CDF2 Fellowship 1023294 to K.K.; and CDF1 Fellowship 1106004 to L.K.M.), the Australian Research Council (CE140100011 and LE110100106; Future Fellowship FT140100278 to A.P.U.), the Leukaemia Foundation of Australia (Postgraduate Scholarship for N.A.G.), the National Heart Foundation of Australia (Future Leader Fellowship for C.A.N.-P.), the Hudson Institute (Star Recruitment Fellowship for M.F.N.) and the Ritchie Centre (Victor Yu Fellowship for M.F.N.).