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

Eur J Immunol. 2014 Jan;44(1):195-203. doi: 10.1002/eji.201343509. Epub 2013 Oct 1.


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.

Keywords: CD161++ T cells; IL-12; IL-18; MAIT cells; T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8 Antigens / metabolism
  • Cell Line
  • Cell Separation
  • Flow Cytometry
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-12 / immunology*
  • Interleukin-12 / pharmacology
  • Interleukin-18 / immunology*
  • Interleukin-18 / pharmacology
  • Lymphocyte Activation
  • Mucous Membrane / immunology*
  • NK Cell Lectin-Like Receptor Subfamily B / metabolism
  • Natural Killer T-Cells / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Receptors, Interleukin-18 / metabolism*
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*


  • CD8 Antigens
  • Interleukin-18
  • NK Cell Lectin-Like Receptor Subfamily B
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Interleukin-18
  • Interleukin-12
  • Interferon-gamma