Characteristics and PD-1 expression of peripheral CD4+CD127loCD25hiFoxP3+ Treg cells in chronic HCV infected-patients

Background: Both regulatory T cells (Tregs) and PD-1/PD-L1 pathway were critically involved in HCV viral persistence. However, the association between them was not well investigated. Herein, we aimed to investigate the distributional profiles of Tregs subsets and association between PD-1 expression on these subsets and development of HCV long-term persistence. Methods: CD45RA and CD27 were employed to separate peripheral Tregs as naive/central memory/effector memory/effector subsets. The phenotypic characteristics and PD-1 expression of Tregs were studied by flow cytometry. Results: In the present study, the majority of Tregs was identified as central memory phenotype in chronic hepatitis C patients compared with nearly equal contribution of naive and central memory subsets in healthy individuals. PD-1 expression was elevated in all CD4+ T cell subset in chronic HCV infected patients, including Tregs. Of note, higher level of PD-1 expression was found on TEM- and effector-Treg than naive- and TCM-Tregs subsets. The ratio of TEM-Tregs/naive-Tregs and TEM-Tregs/TCM-Tregs regarding to PD-1 MFI were significantly lower in CHC patients compared to controls. Conclusions: Our study indicated that distinctive characteristics of PD-1 expression on Tregs in HCV infection suggests associated with impaired adaptive immunity as well as viral long-term persistence. The cross talk between Treg cells and PD-1 induced inhibition in chronic HCV infection deserved further exploration for HCV infection associated immune pathogenesis.