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

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 inhibito...

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Published in:ImmunoHorizons 2020-01, Vol.4 (1), p.14-22
Main Authors: Berkson, Julia D, Slichter, Chloe K, DeBerg, Hannah A, Delaney, Martha A, Woodward-Davis, Amanda S, Maurice, Nicholas J, Lwo, Yu, Ko, Alex, Hsu, Jessica, Chiu, Yu-Wen, Linsley, Peter S, Dixon, Douglas, Prlic, Martin
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Language:English
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Summary: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.
ISSN:2573-7732
2573-7732
DOI:10.4049/immunohorizons.1900061