PD‐1 modulates regulatory T cells and suppresses T‐cell responses in HCV‐associated lymphoma

Abstract

T regulatory (TR) cells suppress T cell responses that are critical in the development of chronic viral infection and associated malignancies. Programmed death-1 (PD-1) also plays a pivotal role in regulation of T cell functions during chronic viral infection. To examine the role of PD-1 pathway in regulating TR cell functions that inhibit T cell responses during virus-associated malignancy, TR cells were investigated in the setting of hepatitis C virus-associated lymphoma (HCV-L), non-HCV-associated lymphoma (non-HCV-L), HCV infection alone, and healthy subjects (HS). Relatively high numbers of CD4+CD25+ and CD8+CD25+ TR cells as well as high levels of PD-1 expressions on these TR cells were found in the peripheral blood of subjects with HCV-L compared to those from non-HCV-L or HCV alone or HS. TR cells from the HCV-L subjects were capable of suppressing the autogeneic lymphocyte response, and depletion of TR cells in PBMC from HCV-L improved T cell proliferation. Additionally, the suppressed T cell activation and proliferation in HCV-L was partially restored by blocking the PD-1 pathway ex vivo, resulting in both a reduction in TR cell number and the ability of TR to suppress the activity of effector T cells. This study suggests that the PD-1 pathway is involved in regulating TR cells that suppress T cell functions in the setting of HCV-associated B cell lymphoma.