Inflammatory Cytokines Induce Sustained CTLA-4 Cell Surface Expression on Human MAIT Cells

Immunohorizons. 2020 Jan 23;4(1):14-22. doi: 10.4049/immunohorizons.1900061.


Mucosal-associated invariant T (MAIT) cells acquire effector function in response to proinflammatory signals, which synergize with TCR-mediated signals. We asked if cell-intrinsic regulatory mechanisms exist to curtail MAIT cell effector function akin to the activation-induced expression of inhibitory receptors by conventional T cells. We examined human MAIT cells from blood and oral mucosal tissues by RNA sequencing and found differential expression of immunoregulatory genes, including CTLA-4, by MAIT cells isolated from tissue. Using an ex vivo experimental setup, we demonstrate that inflammatory cytokines were sufficient to induce CTLA-4 expression on the MAIT cell surface in the absence of TCR signals. Even brief exposure to the cytokines IL-12, IL-15, and IL-18 was sufficient for sustained CTLA-4 expression by MAIT cells. These data suggest that control of CTLA-4 expression is fundamentally different between MAIT cells and conventional T cells. We propose that this mechanism serves to limit MAIT cell-mediated tissue damage.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Surface / immunology*
  • Blood / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • CTLA-4 Antigen / immunology*
  • Cytokines / immunology*
  • Female
  • Gene Expression / immunology
  • Humans
  • Inflammation / genetics
  • Male
  • Middle Aged
  • Mucosal-Associated Invariant T Cells / immunology*
  • Mucous Membrane / immunology
  • Receptors, Antigen, T-Cell / immunology


  • Antigens, Surface
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Cytokines
  • Receptors, Antigen, T-Cell