tetano
Editor, Senior Moderator
Eur J Immunol. 2019 Oct 13. doi: 10.1002/eji.201948279. [Epub ahead of print] [h=1]Type I interferons are important co-stimulatory signals during T cell receptor mediated human MAIT cell activation.[/h]
Lamichhane R[SUP]1[/SUP], Galvin H[SUP]1[/SUP], Hannaway RF[SUP]1[/SUP], de la Harpe SM[SUP]2[/SUP], Munro F[SUP]3[/SUP], Tyndall JD[SUP]2[/SUP], Vernall AJ[SUP]2[/SUP], McCall JL[SUP]3[/SUP], Husain M[SUP]1[/SUP], Ussher JE[SUP]1,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h] 1 Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand. 2 School of Pharmacy, University of Otago, Dunedin, New Zealand. 3 Department of Surgical Sciences, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand. 4 Southern Community Laboratories, Dunedin, 9016, Otago, New Zealand.
[h=3]Abstract[/h] Mucosal associated invariant T (MAIT) cells are abundant unconventional T cells which can be stimulated either via their T cell receptor (TCR) or by innate cytokines. The MAIT cell TCR recognises a pyrimidine ligand, derived from riboflavin synthesising bacteria, bound to MR1. In infection, bacteria not only provide the pyrimidine ligand but also co-stimulatory signals, such as Toll-like receptor agonists, that can modulate TCR-mediated activation. Recently, type I interferons (T1-IFNs) have been identified as contributing to cytokine-mediated MAIT cell activation. However, it is unknown whether T1-IFNs also have a role during TCR-mediated MAIT cell activation. In this study, we investigated the co-stimulatory role of T1-IFNs during TCR-mediated activation of MAIT cells by the MR1 ligand 5-amino-6-D-ribitylaminouracil/methylglyoxal (5-A-RU/MG). We found that T1-IFNs were able to boost interferon-γ and granzyme B production in 5-A-RU/MG-stimulated MAIT cells. Similarly, influenza virus-induced T1-IFNs enhanced TCR-mediated MAIT cell activation. An essential role of T1-IFNs in regulating MAIT cell activation by riboflavin synthesising bacteria was also demonstrated. The co-stimulatory role of T1-IFNs was also evident in liver-derived MAIT cells. T1-IFNs acted directly on MAIT cells to enhance their response to TCR stimulation. Overall, our findings establish an important immunomodulatory role of T1-IFNs during TCR-mediated MAIT cell activation. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[h=4]KEYWORDS:[/h] Mucosal associated invariant T cells; TCR activation; co-stimulation; influenza virus; type I interferons
PMID: 31608441 DOI: 10.1002/eji.201948279
Lamichhane R[SUP]1[/SUP], Galvin H[SUP]1[/SUP], Hannaway RF[SUP]1[/SUP], de la Harpe SM[SUP]2[/SUP], Munro F[SUP]3[/SUP], Tyndall JD[SUP]2[/SUP], Vernall AJ[SUP]2[/SUP], McCall JL[SUP]3[/SUP], Husain M[SUP]1[/SUP], Ussher JE[SUP]1,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h] 1 Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand. 2 School of Pharmacy, University of Otago, Dunedin, New Zealand. 3 Department of Surgical Sciences, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand. 4 Southern Community Laboratories, Dunedin, 9016, Otago, New Zealand.
[h=3]Abstract[/h] Mucosal associated invariant T (MAIT) cells are abundant unconventional T cells which can be stimulated either via their T cell receptor (TCR) or by innate cytokines. The MAIT cell TCR recognises a pyrimidine ligand, derived from riboflavin synthesising bacteria, bound to MR1. In infection, bacteria not only provide the pyrimidine ligand but also co-stimulatory signals, such as Toll-like receptor agonists, that can modulate TCR-mediated activation. Recently, type I interferons (T1-IFNs) have been identified as contributing to cytokine-mediated MAIT cell activation. However, it is unknown whether T1-IFNs also have a role during TCR-mediated MAIT cell activation. In this study, we investigated the co-stimulatory role of T1-IFNs during TCR-mediated activation of MAIT cells by the MR1 ligand 5-amino-6-D-ribitylaminouracil/methylglyoxal (5-A-RU/MG). We found that T1-IFNs were able to boost interferon-γ and granzyme B production in 5-A-RU/MG-stimulated MAIT cells. Similarly, influenza virus-induced T1-IFNs enhanced TCR-mediated MAIT cell activation. An essential role of T1-IFNs in regulating MAIT cell activation by riboflavin synthesising bacteria was also demonstrated. The co-stimulatory role of T1-IFNs was also evident in liver-derived MAIT cells. T1-IFNs acted directly on MAIT cells to enhance their response to TCR stimulation. Overall, our findings establish an important immunomodulatory role of T1-IFNs during TCR-mediated MAIT cell activation. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[h=4]KEYWORDS:[/h] Mucosal associated invariant T cells; TCR activation; co-stimulation; influenza virus; type I interferons
PMID: 31608441 DOI: 10.1002/eji.201948279