@article{21e823a9447e45aea802dd5cf7ea16f4,
title = "Inflammatory Cytokines Induce Sustained CTLA-4 Cell Surface Expression on Human MAIT Cells",
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.",
author = "Berkson, {Julia D.} and Slichter, {Chloe K.} and DeBerg, {Hannah A.} and Delaney, {Martha A.} and Woodward-Davis, {Amanda S.} and Maurice, {Nicholas J.} and Yu Lwo and Alex Ko and Jessica Hsu and Chiu, {Yu Wen} and Linsley, {Peter S.} and Douglas Dixon and Martin Prlic",
note = "Funding Information: Received for publication October 17, 2019. Accepted for publication January 8, 2020. Address correspondence and reprint requests to: Dr. Martin Prlic, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, E5-110, P.O. Box 19024, Seattle, WA 98109-1024. E-mail address: mprlic@fhcrc.org ORCIDs: 0000-0002-5263-158X (H.A.D.); 0000-0002-8465-9958 (M.A.D.); 0000-0002-6901-8271 (A.S.W.-D.); 0000-0002-2667-472X (N.J.M.); 0000-0002-1713-5636 (A.K.); 0000-0003-0911-3717 (D.D.); 0000-0002-0685-9321 (M.P.). 1J.D.B. and C.K.S. equally contributed. This work was supported by National Institute of Health Grants R21 DE026565 (to M.P., D.D.), T32 GM007270 (to J.D.B.), T32 AI007509 (to C.K.S.), T32 A107140 (to A.S.W.-D.), and F99 CA245735 (to N.J.M.). Abbreviations used in this article: MAIT, mucosal-associated invariant T; OM, oral mucosal tissue; RNA-seq, RNA sequencing; Treg, regulatory T cell. The online version of this article contains supplemental material. This article is distributed under the terms of the CC BY-NC 4.0 Unported license. Copyright {\textcopyright} 2020 The Authors Funding Information: This work was supported by National Institute of Health Grants R21 DE026565 (to M.P., D.D.), T32 GM007270 (to J.D.B.), T32 AI007509 (to C.K.S.), T32 A107140 (to A.S.W.-D.), and F99 CA245735 (to N.J.M.). The MR1 tetramer technology was developed jointly by Dr. James McCluskey, Dr. Jamie Rossjohn, and Dr. David Fairlie, and the material was produced by the National Institutes of Health Tetramer Core Facility, as permitted to be distributed by the University of Melbourne. Publisher Copyright: Copyright {\textcopyright} 2020 The Authors",
year = "2020",
month = jan,
day = "1",
doi = "10.4049/immunohorizons.1900061",
language = "English (US)",
volume = "4",
pages = "14--22",
journal = "ImmunoHorizons",
issn = "2573-7732",
publisher = "NLM (Medline)",
number = "1",
}