A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage.
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.
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
Hui-Fern
HF
Koay
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.|Cancer Immunology Research Program, Peter MacCallum Cancer Centre, East Melbourne, Australia.
Nicholas A
NA
Gherardin
John Curtin School of Medical Research, Department of Immunology, Canberra, Australia.
Anselm
http://orcid.org/0000-0001-5933-6463
A
Enders
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
Liyen
L
Loh
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.|Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne, Melbourne, Australia.
Laura K
LK
Mackay
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
Catarina F
CF
Almeida
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
Brendan E
BE
Russ
Department of Paediatrics, Monash University, Clayton, Australia.|The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Australia.
Claudia A
CA
Nold-Petry
Department of Paediatrics, Monash University, Clayton, Australia.|The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Australia.
Marcel F
MF
Nold
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
Sammy
S
Bedoui
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
Zhenjun
Z
Chen
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
Alexandra J
AJ
Corbett
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
Sidonia B G
http://orcid.org/0000-0003-0766-171X
SB
Eckle
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
Bronwyn
B
Meehan
Royal Children's Hospital, Flemington Road, Parkville, Australia.
Yves
Y
d'Udekem
Royal Children's Hospital, Flemington Road, Parkville, Australia.
Igor E
IE
Konstantinov
Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg, Australia.|Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Australia.
Martha
M
Lappas
Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.|Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Queensland, Brisbane, Australia.
Ligong
http://orcid.org/0000-0002-2693-1896
L
Liu
John Curtin School of Medical Research, Department of Immunology, Canberra, Australia.
Chris C
http://orcid.org/0000-0001-5296-6155
CC
Goodnow
Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.|Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Queensland, Brisbane, Australia.
David P
DP
Fairlie
Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Australia.|Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff, UK.|Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, Australia.
Jamie
J
Rossjohn
St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
Mark M
MM
Chong
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
Katherine
K
Kedzierska
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.|Collaborative Research Network, Federation University, Ballarat, Australia.|Fiona Elsey Cancer Research Institute, Ballarat, Australia.
Stuart P
SP
Berzins
The Division of Molecular Immunology, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
Gabrielle T
GT
Belz
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
James
J
McCluskey
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.|Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne, Melbourne, Australia.
Adam P
AP
Uldrich
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.|Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne, Melbourne, Australia.
Dale I
http://orcid.org/0000-0002-3009-5472
DI
Godfrey
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.|Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne, Melbourne, Australia.
Daniel G
DG
Pellicci
D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics; D015415:Biomarkers; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D016130:Immunophenotyping; D054503:Lymphoid Progenitor Cells / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics; D000072336:Mucosal-Associated Invariant T Cells / Q000166:cytology* / Q000502:physiology*; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism*
D055610:Antigens, CD1d; D015415:Biomarkers; D035683:MicroRNAs
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