Efficient presentation of exogenous antigen by liver endothelial cells to CD8(+) T cells results in antigen-specific T-cell tolerance

Myeloid antigen-presenting cells (APC) are known to cross-present exogenous antigen on major histocompatibility class I molecules to CD8(+) T cells an d thereby induce protective immunity against infecting microorganisms. Here we report that liver sinusoidal endothelial cells (LSEC) are organ-residen t, non-myeloid APC capable of cross-presenting soluble exogenous antigen to CD8(+) T cells. Though LSEC employ similar molecular mechanisms for cross- presentation as dendritic cells, the outcome of cross-presentation by LSEC is CD8(+) T cell tolerance rather than immunity. As uptake of circulating a ntigens into LSEC occurs efficiently in vivo, it is likely that cross-prese ntation by LSEC contributes to CD8(+) T cell tolerance observed in situatio ns where soluble antigen is present in the circulation.