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.