CD161++CD8+ T cells, including the MAIT cell subset, are specifically activated by IL‐12+IL‐18 in a TCR‐independent manner

JE Ussher, M Bilton, E Attwod… - European journal of …, 2014 - Wiley Online Library
JE Ussher, M Bilton, E Attwod, J Shadwell, R Richardson, C de Lara, E Mettke, A Kurioka…
European journal of immunology, 2014Wiley Online Library
CD 161++ CD 8+ 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 (V α7. 2)‐J α33 TCR, and IL‐18 R α. 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 CD 161++ CD 8+ T‐cell population is the primary T‐cell population triggered by this
mechanism. Both CD 161++ V α7. 2+ and CD 161++ V α7. 2− T‐cell subsets responded to IL …
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.
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