Type I interferons are important co-stimulatory signals during T cell receptor mediated human MAIT cell activation
| Autor: | Henry D. Galvin, Andrea J. Vernall, James E. Ussher, John L. McCall, Sara M. de la Harpe, Matloob Husain, Joel Da Tyndall, Rajesh Lamichhane, Fran Munro, Rachel F. Hannaway |
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| Rok vydání: | 2019 |
| Předmět: |
Granzyme B production
Immunology T-cell receptor Cell Receptors Antigen T-Cell Stimulation Mucosal associated invariant T cell Biology Ligand (biochemistry) Ligands Lymphocyte Activation Immunity Innate Mucosal-Associated Invariant T Cells Cell biology Interferon-gamma medicine.anatomical_structure Co-stimulation Interferon Type I medicine Immunology and Allergy Cytokines Humans Cell activation Cells Cultured |
| Zdroj: | European journal of immunologyReferences. 50(2) |
| ISSN: | 1521-4141 |
| Popis: | Mucosal associated invariant T (MAIT) cells are abundant unconventional T cells that can be stimulated either via their 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 TLR 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. We found that T1-IFNs were able to boost interferon-γ and granzyme B production in 5-amino-6-d-ribitylaminouracil/methylglyoxal-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. |
| Databáze: | OpenAIRE |
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