title: Human MAIT and CD8αα cells develop from a pool of type-17 precommitted CD8+ T cells.
abstract: Human mucosal associated invariant T (MAIT) CD8(+) and Tc17 cells are important tissue-homing cell populations, characterized by high expression of CD161 ((++)) and type-17 differentiation, but their origins and relationships remain poorly defined. By transcriptional and functional analyses, we demonstrate that a pool of polyclonal, precommitted type-17 CD161(++)CD8αβ(+) T cells exist in cord blood, from which a prominent MAIT cell (TCR Vα7.2(+)) population emerges post-natally. During this expansion, CD8αα T cells appear exclusively within a CD161(++)CD8(+)/MAIT subset, sharing cytokine production, chemokine-receptor expression, TCR-usage, and transcriptional profiles with their CD161(++)CD8αβ(+) counterparts. Our data demonstrate the origin and differentiation pathway of MAIT-cells from a naive type-17 precommitted CD161(++)CD8(+) T-cell pool and the distinct phenotype and function of CD8αα cells in man.
authors.affiliation: Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, United Kingdom.
authors.forename: Lucy J
authors.initials: LJ
authors.lastname: Walker
authors.forename: Yu-Hoi
authors.initials: YH
authors.lastname: Kang
authors.forename: Matthew O
authors.initials: MO
authors.lastname: Smith
authors.forename: Hannah
authors.initials: H
authors.lastname: Tharmalingham
authors.forename: Narayan
authors.initials: N
authors.lastname: Ramamurthy
authors.forename: Vicki M
authors.initials: VM
authors.lastname: Fleming
authors.forename: Natasha
authors.initials: N
authors.lastname: Sahgal
authors.forename: Alistair
authors.initials: A
authors.lastname: Leslie
authors.forename: Ye
authors.initials: Y
authors.lastname: Oo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Geremia
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Scriba
authors.forename: Willem A
authors.initials: WA
authors.lastname: Hanekom
authors.forename: Georg M
authors.initials: GM
authors.lastname: Lauer
authors.forename: Olivier
authors.initials: O
authors.lastname: Lantz
authors.forename: David H
authors.initials: DH
authors.lastname: Adams
authors.forename: Fiona
authors.initials: F
authors.lastname: Powrie
authors.forename: Eleanor
authors.initials: E
authors.lastname: Barnes
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
mesh_terms: D000328:Adult; D017951:Antigen Presentation; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005312:Fetal Blood / Q000276:immunology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D007231:Infant, Newborn; D020411:Oligonucleotide Array Sequence Analysis; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016827:CD8 Antigens; D016207:Cytokines; D020033:Protein Isoforms; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell
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