PT - JOURNAL ARTICLE AU - Joshua Wallington AU - Anthony P. Williams AU - Karl J. Staples AU - Tom M.A. Wilkinson TI - Cytotoxic responses of mucosal-associated Invariant T cells to NTHi infection AID - 10.1183/13993003.congress-2016.PA2621 DP - 2016 Sep 01 TA - European Respiratory Journal PG - PA2621 VI - 48 IP - suppl 60 4099 - http://erj.ersjournals.com/content/48/suppl_60/PA2621.short 4100 - http://erj.ersjournals.com/content/48/suppl_60/PA2621.full SO - Eur Respir J2016 Sep 01; 48 AB - The airways of patients with COPD are commonly colonised by non-typeable Haemophilus influenzae (NTHi). Despite being increased in the COPD airway, CD8+ T cells appear unable to clear NTHi infection, contributing to exacerbations of COPD and promoting disease progression. The CD8+ population in the lung includes recently discovered mucosal-associated invariant T (MAIT) cells, which are activated by the MAIT antigen presenting molecule, MR1.The aim of this study was to determine whether MAIT cells express cytotoxic markers in response to NTHi and may therefore be capable of killing NTHi-infected cells.Monocyte-derived macrophages (MDM) were exposed to live NTHi for 2 h. Infected MDM were then co-cultured with autologous T cells for 5 h or 22 h either alone or in the presence of MR1 blocking antibodies. MAIT cytotoxic and cytokine responses were measured by flow cytometry. ELISA of NTHi-infected MDM supernatant was performed to detect IL-12.Activated MAIT cells showed a statistically significant 2.4-fold increase in intracellular granzyme B and a significant 2-fold upregulation of surface CD107a (both P=0.0039). Blocking of MR1 partially reduced cytokine expression and cytotoxic activity of MAIT cells, suggesting that MAIT activation in this co-culture model is also driven by other factors.Infected MDM produced statistically significant (P<0.01) amounts of IL-12,a cytokine known to induce non-specific activation of MAIT cells. We postulate that activation of MAIT cells by NTHi-infected MDM may also be driven by IL-12.MAIT cells show cytotoxic activity in response to NTHi, but the full mechanism behind MAIT activation remains to be characterised.