Expression of E-cadherin by large CD103+ CD69+ CD8+ T cells promotes their invasion into biliary epithelial cells

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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 of mechanism of CD8+ T cell entry into BEC. CD8+ T cells observed within BEC were large, eccentric, and expressed E-cadherin, CD103 and CD69. Internalisation required cytoskeletal rearrangements which facilitated contact with BEC. Internalised CD8+ T cells were observed in both non-cirrhotic and diseased liver tissues but enriched in PBC patients. 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. E-cadherin+ CD8+ T cells were larger than E-cadherin- CD8+ T cells and invaded BEC more frequently. Overall, we unveil a distinct cell-in-cell structure in the liver detailing the invasion of E-cadherin+ CD103+ CD69+ CD8+ cells T cells into BEC.

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