Figure 2.

Crosstalk between alloreactive T cells and LSECs. LSECs constitute a unique vascular bed with fenestrae organized in sieve plates without basal membrane in the liver. They are the most powerful scavenger system by expression of pattern recognition receptors (PRRs), notably the mannose receptor (MR). On one hand, LSECs process and transfer the MHC-I to the naïve CD8 T cells, which is called “cross-dressing.” This priming process upregulates expression of the co-inhibitory molecule B7-H1(PDL1) on LSECs, whereas the expression of co-stimulatory molecule CD80/CD86 is not changed, thus the binding leads to the apoptosis of the alloreactive CD8 T cells. The LSECs induced tolerance is also highly correlated with antigen load and the strength of TCR stimulation. On the other hand, LSECs also prime naïve CD4 T cells with expression of MHC-II, especially under the inflammatory conditions, but fail to stimulate the proliferation of these cells due to the low expression of co-stimulatory molecules. LSECs also regulate the fate of naïve CD4 T cell differentiation within the liver graft. They suppress the differentiation of Th1 and Th17 cells but favor the enrichment of immune suppressive Th2 and Tregs, which promote the allograft tolerance.