A hepatic network of dendritic cells mediates CD4 T cell help outside lymphoid organs

Abstract While CD4 + T cells are a prerequisite for CD8 + T cell-mediated protection against intracellular hepatotropic pathogens, the mechanisms facilitating the transfer of CD4-help to intrahepatic CD8 + T cells are unknown. Here, we developed an experimental system to investigate cognate CD4 + and CD8 + T cell responses to a model-antigen expressed de novo in hepatocytes and reveal that after initial priming, effector CD4 + and CD8 + T cells migrate into portal tracts and peri-central vein regions of the liver where they cluster with type-1 conventional dendritic cells. These dendritic cells are locally licensed by CD4 + T cells and expand the number of CD8 + T cells in situ, resulting in larger effector and memory CD8 + T cell pools. These findings reveal that CD4 + T cells promote intrahepatic immunity by amplifying the CD8 + T cell response via peripheral licensing of hepatic type-1 conventional dendritic cells and identify intrahepatic perivascular compartments specialized in facilitating effector T cell-dendritic cell interactions.