Myeloid dendritic cells (mDCs) are the most potent professional antigen-presenting cells that regulate specific T-cell responses. Here we studied the ability of mDCs to kill T cells during HCV infection. We found that mDCs from chronic hepatitis C (CHC) patients expressed upregulated levels of two inhibitory ligands, Fas ligand and the ligand 2 of PD-1 (PD-L2), compared to healthy mDCs. However, their expression of the ligand 1 of PD-1 (PD-L1), tumor necrosis factor-related apoptosis inducing ligand (TRAIL), and B lymphocyte stimulator (BLyS) on the cell surface was comparable to healthy mDCs. CHC patient mDCs had cytotoxic effects on autologous patient T cells and allogeneic healthy T cells. CHC patient T cells had increased expression of PD-1 compared to healthy T cells. These results indicate that the cytotoxic activity of mDCs is upregulated to kill T cells during chronic HCV infection, which represents a novel mechanism of HCV immune evasion.
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