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Therapeutic Hope for Patients with Chronic Viral Hepatitis

Aug 23, 2017 3:09:11 PM / by Stacy Matthews Branch, DVM, PhD

Hepatitis C virus model, 3D illustration. A virus consists of a protein coat capsid surrounding RNA and outer lipoprotein envelope with two types of glycoprotein spikes, E1 and E2Hepatitis 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

Topics: Cytotoxic T Cells, Infectious Disease

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