Journal
IMMUNOLOGICAL INVESTIGATIONS
Volume 40, Issue 3, Pages 243-264Publisher
INFORMA HEALTHCARE
DOI: 10.3109/08820139.2010.534218
Keywords
T cells; B cells; PD-1; SOCS-1; immune dysregulation; HCV; lymphoma
Categories
Funding
- ETSU [07-002M]
- NIH NIAID [R15AI072750, 1R15A1084057-01]
- China Scholarship Council [CSC 2008655005]
- Guangzhou Municipal Health Bureau, China
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R15AI072750] Funding Source: NIH RePORTER
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available