T cell dysregulation reflects disease stage in hepatitis virus and alcohol-related liver disease

Liver cirrhosis is characterized by both immunodeficiency and an exaggerated immune response leading to systemic inflammation. In this study, we investigated the role of T cells in different stages of liver disease and therefore analyzed 72 patients stratified into those with and without cirrhosis and compensated and decompensated cirrhosis. Flow cytometry revealed that 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 those patients. In addition, the phenotype of CD4⁺ and CD8⁺ T cells shifted towards activated and exhausted effector-memory and terminally differentiated cells in patients with compensated liver cirrhosis, which was parallelled by an impaired functional response upon stimulation with IL-12 + IL-18. Conversely, in patients with decompensated cirrhosis, CD4⁺ and CD8⁺ T cells exhibited heightened proliferative activity and showed a relative loss of activation and exhaustion marker expression compared with compensated cirrhosis. Furthermore, investigation of 64 soluble immune mediators revealed an inflammatory cytokine milieu in patients with decompensated liver cirrhosis. Taken together, these results indicate an association between phenotypic and functional changes in the T cell compartment and the different stages of liver disease.