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PD-1 Modulates Regulatory T Cells and Suppresses T-Cell Responses in Hcv-Associated Lymphoma

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.

Identiferoai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-17722
Date01 May 2011
CreatorsNi, 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., Yao, Zhi Q.
PublisherDigital Commons @ East Tennessee State University
Source SetsEast Tennessee State University
Detected LanguageEnglish
Typetext
SourceETSU Faculty Works

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