γδ T Cell Therapy Development for Rheumatoid Arthritis (RA)

More and more evidence indicates that γδ T cells may be an excellent target for regulating the immune response of human diseases. Enhancing the function of γδ T cells may provide the possibility to formulate new immunotherapies, which may affect the immune control of various diseases, including Rheumatoid Arthritis (RA). Based on the understanding of γδ T cells in the development of RA disease, inhibitory γδ T cells may have the main therapeutic potential to control this autoimmune disease.

Introduction to RA

RA is an autoimmune disease that can cause joint pain and damage to the entire body. Unlike the wear and tear of osteoarthritis, RA affects the joint lining, causing painful swelling, which ultimately leads to bone erosion and joint deformities. The inflammation associated with rheumatoid arthritis can also damage other parts of the body. Although new drugs have greatly improved treatment options, severe RA can still cause physical disability. Therefore, the development of novel treatment strategies is also crucial for RA.

γδ T Cells as Friends in the Development of RA

So far, the pathogenesis of RA is unclear. As a subgroup of T cells, γδ T cells have many biological functions and are related to many diseases. Studies have shown that Vγ9Vδ2 T cells (the main subtype of peripheral blood γδ T cells) can be activated by isopentenyl pyrophosphate, continuously proliferate and differentiate into effector memory cells. Effector memory Vγ9Vδ2 T cells have the phenotypic characteristics of specific antigen presenting cells, including the high expression of human leucocyte antigen (HLA-DR) and CD80/86. These Vγ9Vδ2 T cells can provide soluble antigens and synthetic peptides to CD4^⁺ T cells. Different phenotypes of Vγ9Vδ2 T cells have different cytokine secretion patterns. Effector memory Vγ9Vδ2 T cells secrete not only interferon (IFN)-γ but also IL-17.

Fig.1 Participation of γδ T cells in RA. (Bank, 2020)

There are a large number of heterogeneous γδ T cells in peripheral blood and synovial fluid of RA patients. These cells are mainly effective memory Vγ9Vδ2 T cells which secrete inflammatory factors. In addition, it was found that γδ T cells had a similar antigen-presenting ability to B cells. These results suggest that in the development of rheumatoid arthritis, γδ T cells secrete cytokines and induce inflammatory cells to participate in the synergistic inflammatory response, aggravate immune dysfunction and produce abnormal immune damage.

What Can We Do?

In order to make better use of γδ T cells to treat RA, we need to understand more about the role of γδ T cells in RA, including antigens recognized by γδ T cells, their development process, activation status and cytokine production, to analyze their role in pathological immune response in RA.

At Creative Biolabs, we have launched a series of γδ T cell related services, including γδ T Cell Development Services, γδ T Cell Receptors Services, and γδ T Cell Engineering Services, to help gain a deeper understanding of this unique T cell population, and hope to provide new ideas for the research of RA disease treatment. If the above services do not meet your requirements, please contact us for your exclusive solution.

Reference

1. Bank, I. The Role of Gamma Delta T Cells in Autoimmune Rheumatic Diseases. Cells. 2020, 9(2): 462.