γδ T Cell Therapy Development for Hepatitis B Virus Infections

Short Introduction to γδ T Cells

γδ T cells are innate immune cells expressing a unique T cell receptor (TCR). They can express Vδ1 chains which are prominent in the intraepithelial layer of mucosal surfaces, where they are involved in maintaining epithelial tissue integrity when facing damage, infection, or transformation, responding to stress antigens on epithelial cells and producing interleukin-10 (IL-10). γδ T cells also express Vδ2 chain, which represents the majority of circulating γδ T lymphocytes in healthy human adults, comprising up to 50%-90% of the peripheral γδ T-cell population. Vδ3 T cells, which are found only a little in blood but are rich in the liver and patients with leukemias and some chronic viral infections. Creative Biolabs provides a wide range of services to accelerate the research of γδ T cells, especially their application in HBV treatment.

Short Introduction of Hepatitis B Virus (HBV) Infection

Viral hepatitis is one of the leading causes of death worldwide with approximately 250 million people being chronically infected with HBV. HBV is a hepatotropic, small, enveloped DNA virus that belongs to the hepadnaviridae family. The virus is noncytopathic but eventually leads to progressive liver fibrosis, cirrhosis, and an increased risk of liver cancer. Nine genotypes (A-I) and several sub-genotypes have been identified with differences in their geographic distribution.

Fig.1 Schematic representation of the HBV life cycle. (Al-Sadeq, 2019)

γδ T Cells and HBV Infection

The liver is rich with multiple innate immune cells and plays an important role in innate immunity in the various stages of liver diseases. Hepatic γδ T cells occupy a small proportion of total liver lymphocytes. In the beginning, the number of Vδ2 T cells, which account for a considerable proportion of γδ T cells in the liver, tends to decline accompanied by disease progression. Nevertheless, Vδ1 T cells are expanded in liver diseases (especially acute-on-chronic liver failure infected by hepatitis B virus) when compared with Vδ2 T cells and defense against liver damage by producing increased cytotoxicity and inflammatory cytokine.

Fig.2 Relationship between antigen persistence and anti-viral T cell responses in the liver. (Fisicaro, 2020)

Researchers revealed that the frequency of γδ T cell subsets (both Vδ1 and Vδ2) has increased in HBV-infected patients without symptoms. In HBV-infected patients, increased effector memory Vδ2 T cells play a protective role by producing interferon γ (IFN-γ). γδ T-cells participate in lymphoid stress surveillance by sensing cellular stress associated with infection, inflammation, and transformation.

The γδ T-cell populations have also been studied in patients with chronic HBV. In patients with chronic HBV, the percentage of Vδ2 T-cells is negatively correlated with serum alanine aminotransferase, aspartate transferase, and bilirubin, suggesting that reduction in the Vδ2 population in the periphery had a role in the chronicity of HBV infection. Also, IFN-γ and TCR-γδ T-cell cytotoxicity were lower in patients with chronic HBV compared to healthy controls.

Fig.3 Nonpeptide antigens for γδ T cell stimulation. (Wu, 2014)

Out Looks

γδ T cells are attractive targets for cellular immunotherapy, but protocols for their therapeutic use need to be optimized. Also, it is necessary to explore better antigens which help us stimulate γδ T cell expansion in vitro for the preparation of many cells for adoptive cell transfer. Future studies should focus on the possible advantages of combining γδ T cell-based immunotherapy with conventional chemotherapy or other therapeutic approaches, such as antiangiogenic drugs. Because γδ T cells can be rapidly activated to lyse infected or malignant cells and to produce effector cytokines such as IFNγ and TNF or IL17, there are ongoing efforts to harness γδ T cells in immunotherapy against cancer and viral infections.

Fig.4 Mechanism underlying γδ T cell recognition of nonpeptide antigens and clinical applications. (Wu, 2014)

Our Services

We offer a variety of services to promote the research of γδ T cells, including but not limited to the following aspects:

• γδ T cell development services (isolation, activation, expansion, characterization, cytotoxicity test, etc.)
• γδ TCR services (TCR repertoires analysis, TCR transcriptome analysis, etc.)
• γδ T cell engineering services

Creative Biolabs has built a team of experienced scientists with specially designed facilities. Our professional scientists will do their best to provide γδ T cells development services to meet every customer's requirements. If you are interested in our γδ T cells services, please contact us or directly sent us an inquiry.

References

1. Al-Sadeq, D. W.; et al. Hepatitis B virus molecular epidemiology, host-virus interaction, coinfection, and laboratory diagnosis in the mena region: an update. Pathogens. 2019, 8(2): 63.
2. Fisicaro, P.; et al. Pathogenetic mechanisms of T cell dysfunction in chronic HBV infection and related therapeutic approaches. Frontiers in Immunology. 2020, 11.
3. Wu, Y. L.; et al. γδ T Cells and their potential for immunotherapy. International Journal of Biological ences. 2014, 10(2): 119-135.