Hepatitis is an inflammation of the liver caused most commonly by hepatitis viruses. Cytotoxic T cells have essential roles in patients with viral hepatitis. Virus-specific cytotoxic T cells can recognize viral antigens of infected liver cells in collaboration with T helper cells. Despite this function in viral hepatitis, the cytotoxic T cell response is nearly undetectable in patients with chronic hepatitis B or C infections.
It is already known that programmed cell death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are immune-related receptors with inhibitory functions that decrease the activation of T cells, and are overexpressed on these T cells during chronic hepatitis and other viral infections. This overexpression of PD-1 and CTLA-4 has been shown to be related to cytotoxic T cell dysfunction. The persistence of hepatitis B and C viruses in chronic infection is associated with T cell dysfunction and overexpression of PD-1 and CTLA-4 liver T cells. However, restoration of cytotoxic T cell function is possible by inhibiting PD-1 or CTLA-4 expression. A review of the current state of knowledge regarding inhibitory immune receptors expressed on virus-specific cytotoxic T cells has been conducted.
Both immune-stimulatory and inhibitory molecules expressed on the surface of T cells help provide the antiviral capacity of the T cells. T cell activation and survival are mediated by CD28 proteins expressed on T cells. However, CD28 is the receptor for proteins expressed on antigen presenting cells, and PD-1 and CTLA-4 belong to the CD28 family of costimulatory molecules. Chronic viral hepatitis infection is linked to the sustained expression of PD-1 and CTLA-4.
Immunotherapy using anti-PD-1 or anti-CTLA-4 monoclonal antibodies in clinical trials has already demonstrated promise as a candidate for treating metastatic melanoma and other tumors. Given the immune function of PD-1 and CTLA-4 in chronic hepatitis, this approach may have utility in patients with this disease. Since cytotoxic T cells from the liver of patients with chronic hepatitis overexpress PD-1 and CTLA-4, and these T cells show virus-specific T-cell dysfunction, blocking PD-1 or CTLA-4 may represent a viable therapeutic approach to recover T cell function and treat chronic viral hepatitis.
If you are undertaking research on hepatitis, we can provide you with high quality cytotoxic T cells and other biomedical products to support your research. Call us today at 877-397-3087 to learn more.
Cho, H., Kang, H., Lee, H., & Kim, C. (2017). Programmed Cell Death 1 (PD-1) and Cytotoxic T Lymphocyte-Associated Antigen 4 (CTLA-4) in Viral Hepatitis. International Journal Of Molecular Sciences, 18(7), 1517. doi:10.3390/ijms18071517