The adhesion of CD8+ T cells to the fenestrated endothelium barrier in the liver sinusoids may differ from their usual pattern of rolling, adhesion and extravasation in other tissues. In Cell, Guidotti et al. use a model of hepatitis B virus infection in mice to show that homing of CD8+ T cells to the liver is independent of selectins, integrins, Gαi protein–coupled chemokine receptors and antigen recognition. Instead, CD8+ T cells use hyaluronan to dock on small islands of CD44+ platelet aggregates that adhere to the liver sinusoid epithelial cells. CD8+ T cells crawl along liver sinusoids and extend cellular protrusions through the endothelial fenestrae to probe the underlying hepatocytes, and recognition of antigen leads to activation of CD8+ T cells and cytokine production before extravasation. Liver fibrosis diminishes sinusoid fenestration, which suggests that it might also impair the immunosurveillance of infected or transformed hepatocytes by T cells.

Cell (23 April 2015) doi:10.1016/j.cell.2015.03.005