Research ArticleT CELLS

IL-23 costimulates antigen-specific MAIT cell activation and enables vaccination against bacterial infection

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Science Immunology  15 Nov 2019:
Vol. 4, Issue 41, eaaw0402
DOI: 10.1126/sciimmunol.aaw0402

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In vivo costimulators for MAIT cells

Mucosal-associated invariant T (MAIT) cells contribute to immune defense against a broad range of pathogens through their ability to recognize microbial riboflavin metabolites presented by the MR1 class I MHC molecule. Wang et al. examined the role that costimulatory signals play in supporting in vivo MAIT cell activation and expansion in mice. Both the inducible T cell costimulator (ICOS) and interleukin-23 (IL-23) costimulatory pathways support MAIT cell expansion and thereby enhance control of infection. A prophylactic vaccine based on combining exogenous IL-23 and a potent MAIT ligand augmented host control of a subsequent pulmonary Legionella infection. These studies pinpoint relevant host costimulatory pathways that can be targeted to enhance MAIT function in antimicrobial defense.

Abstract

Mucosal-associated invariant T (MAIT) cells are activated in a TCR-dependent manner by antigens derived from the riboflavin synthesis pathway, including 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU), bound to MHC-related protein-1 (MR1). However, MAIT cell activation in vivo has not been studied in detail. Here, we have found and characterized additional molecular signals required for optimal activation and expansion of MAIT cells after pulmonary Legionella or Salmonella infection in mice. We show that either bone marrow–derived APCs or non–bone marrow–derived cells can activate MAIT cells in vivo, depending on the pathogen. Optimal MAIT cell activation in vivo requires signaling through the inducible T cell costimulator (ICOS), which is highly expressed on MAIT cells. Subsequent expansion and maintenance of MAIT-17/1-type responses are dependent on IL-23. Vaccination with IL-23 plus 5-OP-RU augments MAIT cell–mediated control of pulmonary Legionella infection. These findings reveal cellular and molecular targets for manipulating MAIT cell function under physiological conditions.

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