title: CD161++ CD8+ T cells, including the MAIT cell subset, are specifically activated by IL-12+IL-18 in a TCR-independent manner.
abstract: CD161(++) CD8(+) T cells represent a novel subset that is dominated in adult peripheral blood by mucosal-associated invariant T (MAIT) cells, as defined by the expression of a variable-α chain 7.2 (Vα7.2)-Jα33 TCR, and IL-18Rα. Stimulation with IL-18+IL-12 is known to induce IFN-γ by both NK cells and, to a more limited extent, T cells. Here, we show the CD161(++) CD8(+) T-cell population is the primary T-cell population triggered by this mechanism. Both CD161(++) Vα7.2(+) and CD161(++) Vα7.2(-) T-cell subsets responded to IL-12+IL-18 stimulation, demonstrating this response was not restricted to the MAIT cells, but to the CD161(++) phenotype. Bacteria and TLR agonists also indirectly triggered IFN-γ expression via IL-12 and IL-18. These data show that CD161(++) T cells are the predominant T-cell population that responds directly to IL-12+IL-18 stimulation. Furthermore, our findings broaden the potential role of MAIT cells beyond bacterial responsiveness to potentially include viral infections and other inflammatory stimuli.
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
authors.forename: James E
authors.initials: JE
authors.lastname: Ussher
authors.forename: Matthew
authors.initials: M
authors.lastname: Bilton
authors.forename: Emma
authors.initials: E
authors.lastname: Attwod
authors.forename: Jonathan
authors.initials: J
authors.lastname: Shadwell
authors.forename: Rachel
authors.initials: R
authors.lastname: Richardson
authors.forename: Catherine
authors.initials: C
authors.lastname: de Lara
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mettke
authors.forename: Ayako
authors.initials: A
authors.lastname: Kurioka
authors.forename: Ted H
authors.initials: TH
authors.lastname: Hansen
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
authors.forename: Christian B
authors.initials: CB
authors.lastname: Willberg
mesh_terms: D016827:CD8 Antigens / Q000378:metabolism; D002460:Cell Line; D002469:Cell Separation; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology* / Q000494:pharmacology; D020382:Interleukin-18 / Q000276:immunology* / Q000494:pharmacology; D008213:Lymphocyte Activation; D009092:Mucous Membrane / Q000276:immunology*; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D053724:Receptors, Interleukin-18 / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*
chemical_list: D016827:CD8 Antigens; D020382:Interleukin-18; D055651:NK Cell Lectin-Like Receptor Subfamily B; D016693:Receptors, Antigen, T-Cell, alpha-beta; D053724:Receptors, Interleukin-18; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: CD161++ T cells; IL-12; IL-18; MAIT cells; T cells
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