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.
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-17722 |
| Date | 01 May 2011 |
| Creators | 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., Yao, Zhi Q. |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Detected Language | English |
| Type | text |
| Source | ETSU Faculty Works |
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