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

Julia D. Berkson, Chloe K. Slichter, Hannah A. DeBerg, Martha A. Delaney, Amanda S. Woodward-Davis, Nicholas J. Maurice, Yu Lwo, Alex Ko, Jessica Hsu, Yu Wen Chiu, Peter S. Linsley, Douglas Dixon, Martin Prlic

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)14-22
Number of pages9
Issue number1
StatePublished - Jan 1 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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