Xiangya Second Hospital Team Discovers Novel Therapeutic Potential of Regulatory T Cells for Autoimmune Diabetes and Develops Antigen Diagnostic Kit

Diabetes is often jokingly referred to as a “disease of affluence,” with its onset frequently linked to excessive and unhealthy dietary habits; however, type 1 diabetes is an exception.

Type 1 diabetes is an autoimmune disease caused by genetic factors or certain viruses,It primarily affects children and adolescents, and there are currently no effective prevention or treatment methods available worldwide. Although the incidence of type 1 diabetes in China is relatively low, the absolute numbers remain alarming given the country’s large population base.According to statistics, in 2021 alone, the number of children and adolescents (aged 0–19) with type 1 diabetes in China reached 56,000, ranking among the highest in the world.

To address this situation, Xiangya Second Hospital of Central South University has established a dedicatedNational Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Ministry of Education), and Hunan Provincial Engineering Research Center for Diabetic Cell Therapy.Under the leadership of Prof. Zhou Zhiguang, Associate Prof. Yu Haibo has been dedicated to research on the diagnosis and treatment of type 1 diabetes.

After more than a decade of research, the laboratory has found thatRegulatory T Cells May See Breakthrough Advances in the Diagnosis and Treatment of Type 1 Diabetes.By chance, Associate Professor Yu Haibo shared with VCBeat’s Orange Bureau how regulatory T cells prevent and treat type 1 diabetes.

As early as a few years ago, Science boldly predicted that regulatory T cells would become the next frontier in cell therapy. This prediction has indeed proven accurate.

Type 1 diabetes is primarily caused by T cells in the patient's body attacking pancreatic beta cells due to immune system dysfunction.Regulatory T cells, as a critical subset of inhibitory T cells in the body, play a vital role in maintaining immune homeostasis. For patients with type 1 diabetes characterized by immune imbalance, regulatory T cells serve as a natural therapeutic agent.

If patient T cells are modulated in vitro to become healthy cells capable of accurately performing immune functions, could this fundamentally resolve type 1 diabetes? Guided by this hypothesis, Professor Yu’s team collaborated in 2012 with Professor Yong Zhao from Hackensack University Medical Center in the United States, pioneering globally the “stem cell education therapy” for children and adolescents (aged 3–18 years) with type 1 diabetes.

Experimental data confirmed that their hypothesis was correct: after undergoing “education,” T cells no longer attacked the pancreas, thereby exerting a therapeutic effect in some patients with type 1 diabetes.

However, after years of clinical trials, the research team found that this approach was not the “optimal solution,” and there remains room for improvement in terms of treatment efficiency and efficacy. Consequently, they began exploring the use of regulatory T cells for the treatment of autoimmune diabetes. Notably, the method employed by Professor Yu’s team to obtain regulatory T cells did not follow the conventional approach of isolating them from peripheral blood.but rather obtained through umbilical cord blood.

The practice has proven to be highly valuable.

On the one hand, regulatory T cells from umbilical cord blood are more readily accessible.During the experiment, it was observed that the number of regulatory T cells in patients was unstable, with many exhibiting functional defects, which significantly compromised therapeutic efficacy. In contrast, regulatory T cells derived from umbilical cord blood are not only far more abundant than those from peripheral blood but also easier to obtain. Furthermore, their in vitro culture and purification efficiencies are remarkably high., and compared with peripheral blood, the culture cost is reduced to 1/100, and the preparation time for treatment is shortened to 1/10.

In addition, in vitro experimental results indicate that umbilical cord blood regulatory T cells haveMore Stable and Superior Immunosuppressive Effects, which has improved treatment efficiency to some extent.

On the other hand, umbilical cord blood regulatory T cells offer higher therapeutic precision.The mechanisms by which umbilical cord blood-derived regulatory T cells modulate immunity are well established, and their therapeutic targets have been clearly elucidated, thereby paving the way for the team’s use of regulatory T cells in the treatment of type 1 diabetes.

Most importantly, the safety of regulatory T cell therapy has been clinically validated.Currently, regulatory T cell therapy has been widely used in clinical practice, including in the fields of graft-versus-host disease and Parkinson's syndrome. Various clinical results have shown that immunotherapy with regulatory T cells does not cause harm to patients' bodies.

After umbilical cord blood-derived regulatory T cells are infused into the patient, they generally become inactivated within 2–3 weeks. This timeframe allows the T cells to exert their immunomodulatory effects while avoiding prolonged immunosuppression or conversion into effector T cells, thereby ensuring patient safety.

Professor Yu told Chengguo Bureau, “To date, more than 40 patients have completed clinical trials of umbilical cord blood regulatory T-cell therapy. Compared with the control group that did not receive regulatory T-cell therapy,”Following treatment, the rate of decline in pancreatic islet function was significantly slowed, demonstrating favorable safety and efficacy.“In the future, we will continue to investigate the role and mechanisms of regulatory T cell combination therapy in enhancing clinical efficacy, striving to bring hope of recovery to more patients with diabetes.”

Now that a new treatment method is available, when is the optimal time to initiate therapy? Professor Yu’s answer is:“The earlier the intervention, the greater the chance of recovery.”

However, in China, due to the diverse types of diabetes, its high degree of insidiousness, and inadequate public health education, many cases of type 1 diabetes are not diagnosed in a timely manner, causing numerous patients to miss the optimal window for treatment.

Professor Yu stated, “Currently, the diagnosis of diabetes largely relies on clinical symptoms for assessment. However, when blood glucose levels are between 7.0 and 10.0 mmol/L, patients may not exhibit clinical symptoms, often leading to misdiagnosis or missed diagnosis in the early stages of diabetes.”

How Can More Patients Be Diagnosed with Diabetes Early and Receive Timely Treatment? Professor Yu believes that, in addition to guiding the public to correctly understand diabetes, convenient, affordable, and accurate diagnostic methods are particularly important.

Based on this,The team invented a new one-step method for preparing GAD65 protein.This breakthrough has resolved the decades-long challenge of the absence of high-quality GAD65 antigen in China, paving the way for the development ofDiabetes Antigen Test Kitlaid a solid foundation. At the same time, it also announced that China's diabetes test kits are no longer completely dependent on overseas imports, and prices can be significantly reduced, alleviating the financial burden on patients.

Moreover, the team has compiled years of dedicated efforts in diabetes research into“The Theory of the Continuous Disease Spectrum of Diabetes”, elucidating the causes of clinical heterogeneity in diabetes, resolving the classification conundrum within the “gray zone” between type 1 and type 2 diabetes, and making multidimensional precision subtyping possible.

Professor Yu stated, “We have fully elucidated the causes of clinical heterogeneity in diabetes. This means that individualized, precision treatment plans can be developed for type 1 diabetes, type 2 diabetes, and even type 1.5 diabetes, which remains difficult to diagnose at present.”

Currently, the regulatory T cell therapy project for type 1 diabetes is at a critical juncture in translating research outcomes into clinical applications. Professor Yu believes that there is still a long way to go from scientific achievements to market entry. This requires policy support from government agencies, academic institutions, and hospitals at all levels, as well as patience from partners and the research team. While continuously updating and upgrading their findings, they must also identify the optimal timing for market entry.