Peritoneal cytokines of patients with decompensated liver cirrhosis drive NK and T cells towards an activated phenotype

Question Liver cirrhosis is the end-stage of every chronic liver disease and patients with advanced cirrhosis have an increased susceptibility to infections and notoriously spontaneous bacterial peritonitis (SBP). The role of the adaptive immunity in this setting remain elusive and presently, less is known regarding the function of lymphocytes in these patients. In this study, we aim to investigate the role of NK cells and T cells in the peritoneal cavity, a common anatomical site for infections in cirrhosis.

Methods Matched peripheral blood and ascites fluid were collected from 46 patients with decompensated cirrhosis, with or without SBP. Phenotype and function of NK cells and T cells were analyzed using high-dimensional flow cytometry and obtained data were compared to blood samples of healthy controls (n=24) and patients with compensated cirrhosis (n=11). Cytokines in matched plasma and ascites were measured using LUMINEX-based multiplex bead assay.

Results Circulating NK cells were elevated in patients with liver cirrhosis and increased even further in the peritoneal cavity in these patients. During SBP, circulating as well as peritoneal NK cell frequencies decreased despite higher proliferative capacity. In contrast, CD8⁺ but not CD4⁺ T cells were enriched in the peritoneal cavity whereas no differences were observed during SBP. In line with this, CD4⁺ and CD8⁺ T cells, as well as NK cells displayed an activated, tissue-resident phenotype in the ascites compared with circulation. This was also corroborated by increased expression of tissue-homing receptors and a higher functional avidity following stimulation with innate-like cytokines. Further, levels of pro-inflammatory cytokines were elevated in ascites fluid compared with plasma.

Conclusions Peritoneal T cells and NK cells are driven towards an activated tissue-resident phenotype and this could be explained by the distinct pro-inflammatory cytokine milieu in the peritoneal cavity.

Publication History

Article published online:
04 January 2021