Liver sinusoidal endothelial cells veto CD8 T cell activation by antigen-presenting dendritic cells.
The liver is known to induce tolerance rather than immunity through tolerogenic antigen presentation or elimination of effector T cells. In particular, hepatic dendritic cells (DC) are known to be little immunogenic for CD8 T cells. Here, we investigated whether this peculiar phenotype resulted from interaction with resident hepatic cell populations. Contact of DC with liver sinusoidal endothelial cells (LSEC) but not hepatocytes or B cells vetoed antigen-presenting DC to fully activate naive CD8 T cells. This MHC-independent regulatory effect of LSEC on DC function was not connected to soluble mediators but required physical contact. Because interaction with third-party LSEC still allowed antigen-presenting DC to stimulate expression of initial activation markers on naive CD8 T cells and to stimulate activated CD8 T cells, we hypothesize that LSEC controlled the DC costimulatory function. Indeed, contact with LSEC led to reduced DC expression levels of CD80/86 or IL-12, but supplementation of these signals failed to rescue the ability to prime naive CD8 T cells, indicating involvement of further molecules. Taken together, our results reveal a novel principle operative in hepatic tolerance induction, in which LSEC not only tolerize T cells themselves but also suppress neighboring APC normally capable of inducing T cell immunity.
Schildberg
Frank A
FA
Institute for Molecular Medicine and Experimental Immunology, Friedrich-Wilhelms-University Bonn, Bonn, Germany.
Hegenbarth
Silke I
SI
Schumak
Beatrix
B
Scholz
Kai
K
Limmer
Andreas
A
Knolle
Percy A
PA
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology; D008099:Liver / Q000098:blood supply* / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D012680:Sensitivity and Specificity