MHC class I transfer from stellate cells to LSEC allows for sinusoidal immunsurveillance

The liver is known for its unique immunological properties. Besides liver parenchymal cells, the hepatocytes, also non-parenchymal cells like dendritic cells, liver-resident macrophages, the Kupffer cells, and liver sinusoidal endothelial cells (LSEC) participate in interaction and modulation of passenger leukocytes. However, little is known on the contribution of stellate cells, non-parenchymal liver cells responsible for contraction of vessel diameter and storage of vitamin A. Because of their location in the space of Dissé stellate cells have no direct contact to circulating lymphocytes.Here we addressed the question if stellate cells contribute to immune regulation by (cross-)presenting exogenous antigen to circulating naive CD8+ T cells and analyzed the outcome of such antigen-presentation. We employed a transgenic mouse model with stellate cell-specific expression of the MHC class I molecule H2-K^b, under the control oft he GFAP-promoter (GFAP-Kb mouse). Using this model system, we found that H2-K^b-restricted CD8 T cells were stimulated in vivo to proliferate and express cytokines suggesting that stellate cells could directly interact with circulating naïve CD8 T cells. However, a detailed characterization of the GFAP-K^b mouse revealed that stellate cells transferred MHC-I molecules to other hepatic cell populations like LSEC. We excluded erratic gene expression driven by GFAP-promoter in LSEC by RT-PCR. Rather, we directly demonstrate transfer of H2-K^b molecules from stellate cells to H2-K^b-negative LSEC. Such molecule-transfer rendered LSEC capable of stimulating H2-K^b-restricted CD8 T cells in an antigen-specific fashion. Our results provide insight into a new mechanism of how local immune regulation in the liver can be achieved, i.e. by transfer of MHC-I molecules from stellate cells to LSEC. Such cross-dressing of antigen-presenting LSEC may contribute to the unique immune functions of the liver.

LSEC - stellate cells