γδ T Cell Therapy Development for Type 1 Diabetes

Compared with most T cells expressing α and β T cell receptor (TCR) chains, γδ T cells are a small part of T cells expressing different TCRs. It can be considered as congenital T cells because it is abundant in skin, respiratory tract, intestinal tract and other tissues in contact with the external environment. Studies have shown that γδ T cells are involved in the immune pathogenesis of autoimmune diseases including T1D in mice models and patients.

Introduction to T1D

T1D, once known as juvenile diabetes or insulin-dependent diabetes, is a chronic disease, in which cell-mediated immune events play a key role in the autoimmune process against pancreatic beta β cells. Insulin is a required hormone to make sugar (glucose) enter cells to produce energy. Different factors, including genetics and some viruses, can cause T1D. Although T1D usually occurs in childhood or adolescence, it can develop in adults. Despite the positive research, there is no cure for it. At present, the main focus of treatment is to control blood glucose levels with insulin, diet and lifestyle to prevent complications.

Fig.1 Overview of the most significant symptoms of diabetes. (Hossain, 2015)

Dual Role of γδ T Cells in the Development of T1D

T cell receptor γδ T cell is a highly conserved lymphocyte lineage, which uses gene rearrangement to encode its defined antigen receptor, and shows non-redundant value in the occurrence of many diseases. The non-obese diabetic (NOD) mouse has been extensively studied as a spontaneous model of human T1D, sharing the characteristics of genetic risk variants and autoimmune pathogenesis with it. However, it is reported that γδ T cells play both a protective role and a pathogenic role in NOD mouse models.

• Protective role: γδ T cells purified from the intraepithelial lymphocyte (IEL) population of NOD mice can prevent T1D when transferred to NOD recipients who have undergone neonatal thymectomy. The transfer of T1D protection by T cells with pre-nebulized insulin depends on the γδ T cells in the inoculum. Recently, it has been reported that γδ T cells protect NOD mice from T1D through a transforming growth factor (TGF)-β-dependent mechanism. These studies support the T1D inhibitory function of γδ T cells in NOD mice.
• Pathogenic role: γδ T cell clones isolated from the spleen and pancreatic lymph nodes (LN) of NOD mice are responsive to insulin, predicting the pathogenic effect of these cells. In addition, in pancreatic islet biopsies from human diabetic patients, the γδ T cell receptor (TCR) sequence is dominant in the confirmed T cell clonotypes, which indicates that γδ T cells infiltrate the islets of human T1D. These data together indicate that γδ T cells may be involved in the pathogenesis of T1D.

What Can We Do for You?

Based on the dual role of γδ T cells in T1D, it can be imagined that regulatory γδ T cells provide a new therapeutic method for the prevention and treatment of T1D. However, more research is needed, particularly to define their biology, to find out whether they are important to humans and, if so, how to target such cells to increase their number.

Based on advanced technology and years of research, Creative Biolabs provides high-quality customized γδ T cell therapy services, covering the entire therapy development process. In particular, we provide a series of γδ T Cell Development Services, γδ T Cell Receptors Services, γδ T Cell Engineering Services, to better understand the relationship between γδ T cells and diseases, and promise to provide the most suitable technology, plan and budget requirements for you to help your γδ T cell therapy development research of T1D. If you want to get more information, please feel free to contact us.

Reference

1. Hossain, R. Evaluation of the efficacy of Alisa Garlitab, an anti-diabetic herbal preparation in streptozotocin induced diabetic rats. 2015, DOI:10.13140/RG.2.1.1986.0643