Differential Regulation of T and B lymphocytes by PD-1 and SOCS-1 signaling in Hepatitis C Virus-associated non-Hodgkin's Lymphoma
| Autor: | Ying Zhang, Penny Thayer, Ashley D. Frazier, Cheng J. Ma, Jonathan P. Moorman, Xiao Y. Wu, Xin Y Chen, Zhi P Dong, Lei Ni, Zhi Q. Yao, Chun L. Zhang, Thomas Borthwick |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male T-Lymphocytes T cell Programmed Cell Death 1 Receptor Immunology Naive B cell Suppressor of Cytokine Signaling Proteins Hepacivirus Biology TCIRG1 Interleukin 21 Antigens CD immune system diseases hemic and lymphatic diseases medicine Humans Cytotoxic T cell B cell Aged B-Lymphocytes Lymphoma Non-Hodgkin ZAP70 virus diseases General Medicine Middle Aged Hepatitis C digestive system diseases Gene Expression Regulation Neoplastic B-1 cell medicine.anatomical_structure Cancer research Apoptosis Regulatory Proteins Signal Transduction |
| Zdroj: | Immunological Investigations. 40:243-264 |
| ISSN: | 1532-4311 0882-0139 |
| DOI: | 10.3109/08820139.2010.534218 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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