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

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

Author information

1
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109.
2
Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA 98195.
3
Department of Global Health, University of Washington, Seattle, WA 98195.
4
Systems Immunology Division, Benaroya Research Institute, Seattle, WA 98101.
5
Zoological Pathology Program, University of Illinois, Brookfield, IL 60513.
6
Department of Periodontics, University of Washington, Seattle, WA 98195; and.
7
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; mprlic@fhcrc.org.
8
Department of Immunology, University of Washington, Seattle, WA 98109.

Abstract

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.

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