Combined activation signalling breaks established CD8+ T cell tolerance and results in effector CTL generation

In the liver, soluble and gut-derived antigens are efficiently taken up by the resident antigen presenting cells, the liver sinusoidal endothelial cells (LSEC). Importantly, LSEC are capable of cross-presenting these antigens on MHC class I molecules to naïve CD8+ T cells. This cross-presentation results in the induction of antigen-specific T cell tolerance and the generation of a unique, tolerant CD8+ T cell subset. LSEC-tolerised CD8+ T cells are incapable of cytotoxic activity or production of effector cytokines. As we investigated the fate of tolerant CD8+ T cells in vivo, we discovered that LSEC-mediated T…