Hepatic stellate cells veto CD8 T cell activation by a CD54-dependent mechanism

The role of the liver in induction of T cell tolerance is achieved by the action of tolerogenic hepatic antigen-presenting cells (APC) and regulatory T cells. Hepatic stellate cells (HSC) are known to have diverse immune functions ranging from immunogenic antigen presentation to induction of T cell apoptosis. Here we report on a novel role of stellate cells vetoing priming of naive CD8 T cells. Murine and human HSCs, but not hepatocytes, prevented activation of naive T cells by dendritic cells, artificial APCs or PMA/Ionomycin in a cell-cell contact dependent mechanism. Veto function directly correlated with HSC-activation and required expression of CD54 independently of B7-H1. HSC veto function was overcome by exogenous IL-2. Our results demonstrate a novel function of HSC in local skewing of immune responses in the liver, preventing initial stimulation of those T cells transmigrating across the sinusoidal barrier. These results indicate a beneficial role in hepatic fibrosis, where increased CD54 expression on HSCs could attenuate further T cell activation. Furthermore, IL-2 was identified as a key cytokine in mediating local T cell immunity to overcome hepatic tolerance.

Fibrosis - Immune regulation - Liver immunology - Tolerance