HOME
Return to Table of Contents
THE PRESENCE OF KILLER DENDRITIC CELLS DURING CHRONIC HCV INFECTION
L Zhao, L Tyrrell
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta
Dendritic cells (DCs) can present antigen in either an immunogenic or a tolerogenic way by expressing activating or inhibitory molecules. In this study, we detected the expression of inhibitory molecules on DCs from chronic HCV-infected patients, and the ability of these DCs to induce T cell apoptosis.
Monocyte-derived DCs from chronic HCV-infected patients and healthy controls were cultured. Their expression of Fas ligand (FasL), ligand 1 of programmed death receptor-1 (PD-L1) and ligand 2 of programmed death receptor-1 (PD-L2) were determined by flow cytometry (FACS). Then DCs were co-cultured with T cells for 5 hours. Cell apoptosis rates were determined by terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling (TUNEL) staining and FACS analysis.
We found that DCs from chronic HCV-infected patients express FasL and PD-L2 at higher levels than those from healthy controls. In contrast, DCs from chronic HCV-infected patients and healthy controls express PD-L1 at comparable levels. In the co-culture assay, cell apoptosis rate was significantly increased in the group where DCs from chronic HCV-infected patients were co-cultured with T cells compared to the group where DCs from healthy controls were co-cultured with T cells. However, when DCs from chronic HCV-infected patients were incubated with a human leukemia T cell line, Jurkat T cells, the apoptosis rate was comparable to those DCs from healthy controls. These results provide support for the concept that DCs from CHC patients may work as killer DCs to induce T cell apoptosis. The incapability of DCs from chronic HCV-infected patients to kill Jurkat T cells may indicate that these patient DCs only kill specific target T cells.
In conclusion, DCs from chronic HCV-infected patients express high levels of inhibitory molecules and may act as killer DCs. This might be a mechanism contributing to impaired T cell responses against HCV infection in chronic carriers of HCV.
This work was supported by CIHR and Li Zhao was funded by NCRTP-HepC.