MR1-ligand induced apoptosis and functional impairment of mucosal associated invariant T (MAIT) cells in patients with rheumatoid arthritis and ankylosing spondylitis (#153)
Mucosal associated invariant T (MAIT) cells are an innate-like lymphocyte population predominant at mucosal sites, which express a semi-invariant T cell receptor restricted to the MHC Class I-like molecule, MR1. MR1 presents ligands derived from the riboflavin synthesis pathway common to a range of bacteria and yeast. There is increasing evidence in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) for microbial dysbiosis, but the mechanisms underlying this disease association are unclear. Here, we studied the frequency of peripheral blood (PB) MAIT cells in arthritis patients and the response to a riboflavin-derivative MAIT-activating ligand (RL-6Me) in vitro. We compared the frequency of CD3+CD4-CD161hiTRAV1-2+ PB MAIT cells in RA and AS patients, and in healthy controls (HC). We analyzed cellular activation in response to RL-6Me. We found no difference in MAIT cell frequencies in HC, RA and AS patient groups. The proportion of PB MAIT cells declined in all groups with age and was significantly lower in patients with late- than early-onset RA. When stimulated with RL-6Me, MAIT cells from RA and AS patients were more susceptible to apoptosis, and residual cells expressed lower levels of CD69, TNF and IFN-gamma than in HC. In conclusion, PB MAIT cells decline with age in arthritis patients similar to HC. MAIT cells of RA and AS patients have a greater susceptibility to MR1 ligand-induced cell death. Surviving cells have a lower capacity for cytokine production. At mucosal sites, this altered MAIT cell function could impact local microbial control.