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Nat Immunol. 2016 Nov;17(11):1300-1311. doi: 10.1038/ni.3565. Epub 2016 Sep 26.

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

Author information

1
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
2
Cancer Immunology Research Program, Peter MacCallum Cancer Centre, East Melbourne, Australia.
3
John Curtin School of Medical Research, Department of Immunology, Canberra, Australia.
4
Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne, Melbourne, Australia.
5
Department of Paediatrics, Monash University, Clayton, Australia.
6
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Australia.
7
Royal Children's Hospital, Flemington Road, Parkville, Australia.
8
Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg, Australia.
9
Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Australia.
10
Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
11
Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Queensland, Brisbane, Australia.
12
Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Australia.
13
Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff, UK.
14
Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, Australia.
15
St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
16
Collaborative Research Network, Federation University, Ballarat, Australia.
17
Fiona Elsey Cancer Research Institute, Ballarat, Australia.
18
The Division of Molecular Immunology, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
19
Department of Medical Biology, University of Melbourne, Parkville, Australia.

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-presenting molecule CD1d, suggestive of a niche shared by MAIT cells and natural killer T cells (NKT cells). Accordingly, this study maps the developmental pathway and checkpoints that control the generation of functional MAIT cells.

PMID:
27668799
DOI:
10.1038/ni.3565
[Indexed for MEDLINE]

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