PD-1 Modulates Regulatory T Cells and Suppresses T-Cell Responses in Hcv-Associated Lymphoma
Document Type
Article
Publication Date
5-1-2011
Description
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 has 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 with 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 peripheral blood mononuclear cells 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.
Citation Information
Ni, Lei; Ma, Cheng J.; Zhang, Ying; Nandakumar, Subhadra; Zhang, Chun L.; Wu, Xiao Y.; Borthwick, Thomas; Hamati, Agnes; Chen, Xin Y.; Kumaraguru, Uday; Moorman, Jonathan P.; and Yao, Zhi Q.. 2011. PD-1 Modulates Regulatory T Cells and Suppresses T-Cell Responses in Hcv-Associated Lymphoma. Immunology and Cell Biology. Vol.89(4). 535-539. https://doi.org/10.1038/icb.2010.121 PMID: 20975732 ISSN: 0818-9641