• Joshua C Wallington, Anthony P Williams, Karl J Staples, and Wilkinson Tom M A TMA Clinical & Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Sout.
• Clinical & Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Southampton, United Kingdom.
• J. Allergy Clin. Immunol. 2018 Jun 1; 141 (6): 2182-2195.e6.

BackgroundBacterial respiratory tract infections and exacerbations of chronic lung diseases are commonly caused by nontypeable Haemophilus influenzae (NTHi). Cell-mediated cytotoxicity might be key to controlling infection, but the responses of NTHi-specific T-cell populations are not well understood. Mucosal-associated invariant T (MAIT) cells are a recently discovered, innate-like subset of T cells with cytotoxic function, the role of which in lung immunity is unclear.ObjectiveThe aim of this study was to determine the mechanisms behind conventional T-cell and MAIT cell cytotoxic responses to NTHi.MethodsHuman ex vivo lung explants were infected with a clinical strain of NTHi. Monocyte-derived macrophages were also infected with NTHi in vitro and cocultured with autologous T cells. Cytotoxic responses of T-cell subsets were measured by using flow cytometry.ResultsWe found significant upregulation of the cytotoxic markers CD107a and granzyme B in lung CD4+, CD8+, and MAIT cell populations. We show that MAIT cell cytotoxic responses were upregulated by a combination of both time-dependent antigen presentation and a novel mechanism through which IL-12 and IL-7 synergistically control granzyme B through upregulation of the IL-12 receptor.ConclusionsOverall, our data provide evidence for a cytotoxic role of MAIT cells in the lung and highlight important differences in the control of adaptive and innate-like T-cell responses. Understanding these mechanisms might lead to new therapeutic opportunities to modulate the antibacterial response and improve clinical outcome.Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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