Mucosal-associated invariant T cells redistribute to the peritoneal cavity during spontaneous bacterial peritonitis and contribute to peritoneal inflammation.

Mucosal-associated invariant T (MAIT) cells are depleted from blood in patients with advanced liver disease and show features of immune dysfunction. As circulating MAIT cells differ from organ-resident MAIT cells, we aimed to investigate the frequency, phenotype, and function of peritoneal MAIT cells from patients with cirrhosis and spontaneous bacterial peritonitis (SBP).MAIT cells in blood and ascitic fluid from patients with cirrhosis were characterized using flow cytometry. Healthy individuals and non-cirrhotic patients undergoing peritoneal dialysis served as controls. MAIT cell migration was studied in transwell assays. Cytokine release in response to infected ascitic fluid and bacterial products was assessed in vitro.Peritoneal CD3+ CD161hi Vα7.2+ T cells had an inflammatory, tissue retention phenotype, expressing the αE integrin, the chemokine receptors CCR5 and CXCR3, and the activation marker CD69 at higher levels than their circulating equivalents. 77% bound to MR1 tetramers loaded with the pyrimidine intermediate 5-OP-RU. The ratio of blood to peritoneal MAIT cell frequency increased from 1.3 in the absence of SBP to 2.6 at diagnosis, and decreased by day 3. MAIT cells migrated towards infected ascitic fluid containing CCL5 and CCL20, and released cytokines in an MR1-restricted fashion. Whereas the depleted circulating MAIT cell pool displayed features of immune exhaustion, peritoneal MAIT cells remained competent producers of inflammatory cytokines in response to bacterial products. Peritoneal MAIT activation correlated with systemic inflammation suggesting a possible link between periteonal and systemic immunity.Peritoneal MAIT cells phenotypically and functionally differ from circulating MAIT cells in decompensated cirrhosis, and redistribute to the peritoneum during SBP.