γδ T Cell Therapy Development for HIV Infections

Targeted therapy utilizing the potent cytotoxic capabilities of γδ T cells is a compelling avenue of research that has broad implications in treating a variety of diseases. Based on the current research, γδ T cells merit further consideration in investigations toward a human immunodeficiency virus (HIV) cure. Based on years of experience in immunotherapy, Creative Biolabs provides our customers with high-quality customized γδ T cell development and engineering services to promote HIV-against research.

Introduction to HIV

Until now, HIV infection remains one of the most challenging health issues worldwide. Despite increasing awareness of the disease and improved access to antiretroviral therapy (ART), approximately 5000 individuals become newly infected every day. The severity of HIV has made scientists never stop studying and challenging it. Recent reports have shown that in addition to infecting and depleting CD4⁺ T cells, HIV infection also has a wide overall effect on the immune system, mediated largely by the phenomenon of microbial translocation. Rapid replication of HIV in gut-associated lymphoid tissue (GALT) results in substantial damage to the gut epithelial barrier and the subsequent translocation of microbial products such as LPS into the circulation. This results in chronic immune activation and, consequently, the dysfunction of conventional, bystander αβ T cells. The upregulation of HLA-DR and CD38 by T cells is associated with chronic immune activation and has proven to be strong predictors of disease progression. Additionally, markers such as PD-1, CD57, and CD100 have been used to define terminally differentiated, exhausted, or dysfunctional T cells and are now the target of immunotherapies aimed at reducing T-cell exhaustion.

Relationship between γδ T Cells and HIV

While HIV is well known to impact the function and distribution of conventional T-cell subsets, the impact of the disease on γδ T-cell subsets has been an ongoing subject of research since the late 1980s. Multiple reports have since described an inversion of the typical Vδ2: Vδ1 T-cell ratio in the peripheral blood of HIV-infected/AIDS patients, which was quickly determined to represent an increase in Vδ1 T-cell frequency and a depletion of Vδ2Vγ9 T cells. Subsequent investigations have focused on the mechanisms behind this expansion/depletion, as well as the relationship of γδ T subsets to HIV disease progression. Approaches to rescue and harness γδ T-cell responses as a means of anti-HIV immunotherapy are the future directions of this rapidly evolving field.

Fig.1 Some of the known functions for human Vδ2 T cells that are related to HIV infection. (Pauza, 2014)

Clinical Research of γδ T-Cell During HIV Infection

γδ T Cells can control HIV replication through multiple mechanisms in vitro, including direct cytotoxicity of infected cells. Vδ2 T cells can be recruited to HIV-infected DCs via CCL4 production, where they control viral replication and reduce HIV transmission to bystander CD4⁺ T cells. β-Chemokine production by both Vδ1 and Vδ2 cells can block HIV infection of target cells. Although HIV elite/viral controllers exhibit Vδ2 depletion relative to healthy controls, they maintain Vδ2 frequencies that are significantly higher than either untreated or ART-treated subjects. These cells predominately exhibit a TCM phenotype and produce more IL-17 than cells from viremic patients.

Services of γδ T Cells at Creative Biolabs

Allogeneic transfer of ex vivo expanded γδ T cells presents an intriguing therapeutic option that may one day bring us a step closer to a sustained ART-free HIV remission or complete cure. Creative Biolabs has many experienced scientists focused on cellular immunotherapies for years. With extensive industrial experience, we provide comprehensive γδ T cells development services for the research of HIV infections and many advantages are listed:

• Comprehensive technology platform with an excellent expert team.
• Extensive experience and hundreds of successful precedents.
• Efficient, accurate, and cost-effective services.

With advantages in various aspects, we are confident that our services will be your best choice. Please contact us for more information.

Reference

1. Pauza, C. D.; et al. Gammadelta t cells in HIV disease: Past, present, and future. Front Immunol. 2014, 5: 687.