Immune activation as a hallmark in liver disease progression

Background & Aims: Liver cirrhosis is characterized by an immune dysfunction on the one hand, and an exaggerated immune response leading to systemic hyperinflammation on the other hand. This so called cirrhosis-associated-immune dysfunction (CAID) involves innate and adaptive immune cells. In this study, we aim to investigate the role of T cells as part of the adaptive immune system in different stages of liver disease.

Methods: In total, 62 patients with liver disease were enrolled in this study and subdivided into patients with and without cirrhosis as well as compensated and decompensated cirrhosis. T cell phenotype and function were analyzed using flow cytometry and cytokines were measured using a bead-based multiplex assay.

Results: CD8+T cells, but not CD4+T cells were diminished in patients with decompensated liver cirrhosis and this further resulted in an increased CD4/CD8 T cell ratio in patients with decompensated cirrhosis. In addition, the phenotype of CD4+and CD8+T cells shifted towards activated and highly proliferative effector-memory and terminally differentiated cells in patients with liver cirrhosis. Furthermore, following stimulation with IL-12+IL-18, CD4+and CD8+T cells from patients with liver cirrhosis responded with higher expression of pro-inflammatory cytokines and effector molecules compared with healthy controls. This was further corroborated by the presence of a pro-inflammatory cytokine milieu in these patients.

Conclusions: CD4+and CD8+T cells in accordance with the soluble immune landscape are skewed towards an activated and pro-inflammatory environment and reveals immune activation as a hallmark in liver disease progression.

Publication History

Article published online:
20 January 2025