OC-011 A novel population of immunosuppressive cd8 t cells is expanded in patients with decompensated liver disease

IntroductionCirrhosis associated immune dysfunction is central to immuneparesis, infection susceptibility and adverse outcome in patients with chronic liver disease (CLD). Whilst defects in innate immune responses are recognised, the role of adaptive immunity in CLD remains unexplored. Regulatory HLADR+ CD8+ T cells are recently shown to possess immunosuppressive properties. Our aims were to determine whether negative regulation of CD8+ T cell responses contribute to impaired antimicrobial responses in CLD.MethodCirculating CD8 subsets from 33 CLD patients (with chronic cirrhosis, acute decompensation (AD) or acute on chronic liver failure (ACLF)) and 14 healthy controls (HC) were determined using flow cytometry and a panel of phenotypic markers to identify naïve, memory (CD45RO, CD45RA, CCR7, CD62L) subsets as well as expression of activation (CD27, CD28), inhibition (CTLA4, PD1) and suppressive (HLADR, CD25, FOXP3) markers. Immunohistochemistry was performed on explant liver tissue (n=8). Functional analyses of CD8+ T cells were performed using anti-CD3 in the presence of allogeneic dendritic cells or CD3/CD28 beads. Suppressive assay were performed using HLA-DR- or + CD8+ T cells in co-culture with autologous CD3/CD28 stimulated PBMCs.ResultsCompared to HC, the proportion of circulating and intrahepatic immunosuppressive HLADR+CD8+ T cells were higher in CLD (mean of 20vs37%;p=0.0002). Immunophenotypic analyses of HLADR+CD8+ T cells identify that these cells are characterised by increased CTLA4 expression compared to HLADR-CD8+ (9.2 vs 0.1%;p