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

Kieran EnglishRain KwanLauren E HolzClaire McGuffogJelte M M KrolDaryan KempeTsuneyasu KaishoWilliam R HeathLeszek LisowskiMaté BiroGeoffrey W McCaughanDavid G BowenPatrick Bertolino
Published in: Nature communications (2024)
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.
Keyphrases
  • dendritic cells
  • regulatory t cells
  • immune response
  • nk cells
  • working memory
  • palliative care
  • liver injury
  • oxidative stress
  • reactive oxygen species
  • heat shock
  • drug induced
  • multidrug resistant