Dr. Alice Long, a Principal Investigator at Benaroya Research Institute, discusses topics such as B cell selection, IBD management, neuropeptides in type 2 immunity, and intestinal antigen recognition. She also explores T cell tolerance in type 1 diabetes, T cell exhaustion in therapy, and the challenges of checkpoint blockade. The hosts and guest also chat about hobbies, scuba diving, and upcoming meetings.
T-cell tolerance plays a crucial role in type 1 diabetes and targeting T cells can delay disease onset and progression.
The association between HLA genes and type 1 diabetes involves antigen processing and presentation, thymic selection, and T-cell receptor signaling.
Current approaches in treating type 1 diabetes include anti-CD3 therapy and potential augmentation of regulatory T-cell populations.
Deep dives
T-cell tolerance and immune regulation in type 1 diabetes
Dr. Alice Long discusses the role of T-cell tolerance and immune regulation in type 1 diabetes. She explains that type 1 diabetes is a T-cell-driven autoimmune disease, with a strong HLA association indicating the involvement of CD4 T cells. Therapies targeting T cells, such as anti-CD3 antibodies, have shown promising results in delaying the onset and progression of type 1 diabetes. Dr. Long also highlights the importance of understanding T-cell exhaustion and its potential role in autoimmunity, including type 1 diabetes. She mentions that while exhaustion is typically associated with negative outcomes in cancer and chronic viral infections, it may have a beneficial correlation in certain autoimmune diseases.
HLA associations in type 1 diabetes
Dr. Alice Long discusses the association between HLA genes and type 1 diabetes. While the exact mechanisms behind this association are still not fully understood, it is thought to involve antigen processing and presentation. The specific HLA alleles may have a higher affinity for presenting self-antigens associated with type 1 diabetes. Dr. Long also mentions the role of thymic selection in determining the autoimmune response and the potential involvement of T-cell receptor signaling and high-affinity TCRs. However, more research is needed to fully uncover the molecular mechanisms.
Treating Type 1 Diabetes and the Challenges
Dr. Alice Long discusses the current approaches in treating type 1 diabetes. She explains that anti-CD3 therapy has shown success in delaying the onset and progression of the disease. However, due to the availability of insulin as a replacement therapy, the bar for immune therapy in type 1 diabetes is higher compared to other autoimmune diseases. Steroids and other broad immunosuppressive drugs are not suitable due to their side effects. Dr. Long also mentions the potential of augmenting regulatory T-cell populations as a therapeutic strategy and highlights the ongoing clinical trials in this area.
T-Cell Exhaustion in Type 1 Diabetes
Dr. Alice Long discusses the concept of T-cell exhaustion in type 1 diabetes. While T-cell exhaustion is typically associated with chronic viral infections and cancer, there is evidence to suggest its involvement in certain autoimmune diseases, including type 1 diabetes. Dr. Long explains that the sustained T-cell receptor signaling and antigen specificity may play a role in driving T-cell exhaustion in type 1 diabetes. She also discusses the potential impact of T-cell exhaustion on disease progression, treatment response, and the need for further research to unravel the molecular mechanisms involved.
Exploring the Deep Sea and Future Research
In a personal aside, Dr. Alice Long shares her hobby of wanting to explore the deep sea and see what lies beneath. She expresses her interest in the mysteries of the deep sea and the life forms that inhabit it. Although she has not pursued scuba diving or submersible exploration yet, she hopes to have the opportunity to see more of the deep sea in the future.
Dr. Alice Long is an Associate Member and Principal Investigator at Benaroya Research Institute at Virginia Mason, where her lab focuses on discovering how tolerance is lost in human autoimmunity and how therapy can restore tolerance.
Insights into B Cell Selection – Antigen-presenting autoreactive B cells play a crucial role in tolerizing T cells and suppressing tissue-specific autoimmune inflammation.
A New Perspective for IBD Management – Researchers discovered a polymorphism encoding a defective fusion protein that is correlated with inflammatory bowel disease severity.
A Neuropeptide in Type 2 Immunity – Scientists show that neuromedin U programs eosinophils to promote mucosal immunity of the small intestine.
