Expression of E-cadherin by CD8+ T cells promotes their invasion into biliary epithelial cells

Abstract

The presence of CD8⁺ T cells in the cytoplasm of biliary epithelial cells (BEC) has been correlated with biliary damage associated with primary biliary cholangitis (PBC). Here, we characterise the mechanism of CD8⁺ T cell invasion into BEC. CD8⁺ T cells observed within BEC were large, eccentric, and expressed E-cadherin, CD103 and CD69. They were also not contained within secondary vesicles. Internalisation required cytoskeletal rearrangements which facilitated contact with BEC. Internalised CD8⁺ T cells were observed in both non-cirrhotic and cirrhotic diseased liver tissues but enriched in PBC patients, both during active disease and at the time of transplantation. E-cadherin expression by CD8⁺ T cells correlated with frequency of internalisation of these cells into BEC. E-cadherin⁺ CD8⁺ T cells formed β-catenin-associated interactions with BEC, were larger than E-cadherin^- CD8⁺ T cells and invaded into BEC more frequently. Overall, we unveil a distinct cell-in-cell structure process in the liver detailing the invasion of E-cadherin⁺ CD103⁺ CD69⁺ CD8⁺ T cells into BEC.