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Differential Regulation of T and B Lymphocytes by pd-1 and SOCS-1 Signaling in Hepatitis C Virus-Associated Non-Hodgkin's Lymphoma

HCV infection is associated with immune dysregulation and B cell Non-Hodgkins lymphoma (HCV-NHL). We have previously shown in vitro that HCV core protein differentially regulates T and B cell functions through two negative signaling pathways, programmed death-1 (PD-1) and suppressor of cytokine signaling-1 (SOCS-1). In this report, we performed a detailed immunologic analysis of T and B cell functions in the setting of HCV-NHL. We observed that T cells isolated from patients with HCV-NHL exhibited an exhausted phenotype including decreased expression of viral-specific and non-specific activation markers; whereas B cells exhibited an activated phenotype including over-expression of cell activation markers and immunoglobulins compared to healthy subjects. Individuals with HCV alone or NHL alone exhibited abnormal T and B cell phenotypes, but to a lesser extent compared to HCV-NHL. This differential activation of T and B lymphocytes was inversely associated with the expression of PD-1 and SOCS-1. Interestingly, blocking PD-1 during TCR activation inhibited SOCS-1 gene expression, suggesting that these regulatory pathways are linked in T cells. Importantly, blocking PD-1 also restored the impaired T cell functions observed in the setting of HCV-NHL. These results support a coordinated mechanism by which HCV might cause immune dysregulation that is associated to HCV-NHL.

Identiferoai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-17723
Date14 March 2011
CreatorsYao, Zhi Q., Ni, Lei, Zhang, Ying, Ma, Cheng J., Zhang, Chun L., Dong, Zhi P., Frazier, Ashley D., Wu, Xiao Y., Thayer, Penny, Borthwick, Thomas, Chen, Xin Y., Moorman, Jonathan P.
PublisherDigital Commons @ East Tennessee State University
Source SetsEast Tennessee State University
Detected LanguageEnglish
Typetext
SourceETSU Faculty Works

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