Dr. Frances Lund, a renowned immunologist known for her research on T cell dysfunction and B cell differentiation, shares her latest findings. They delve into the impacts of lactate metabolism on exhausted T cells and the fascinating role of mitochondria in immune dynamics. The discussion highlights novel pathways of B cell responses that operate independently of T cells, offering insights into autoimmune diseases and vaccine development. They wrap up the conversation with reflections from the IMMUNOLOGY2024 conference.
Research on the MCT11 lactate transporter reveals its critical role in T cell exhaustion, suggesting potential therapeutic targets in cancer treatment.
Extra follicular B cell responses, independent of T cell guidance, highlight their significance in memory generation and possible links to autoimmune diseases.
Deep dives
Immunometabolism and T Cell Exhaustion
Research on immunometabolism highlights the role of the MCT11 lactate transporter in T cell exhaustion. A study presented by Ronel Peralotta showed that exhausted T cells have a greater capacity to uptake lactic acid compared to regular T cells, which is mediated by MCT11. The findings suggest that inhibiting this transporter can improve outcomes in mouse tumor models, potentially breaking the cycle of T cell exhaustion caused by chronic lactate exposure. This underscores the intricate relationship between metabolic adaptations in T cells and their functional capacities in tumor environments.
Mitochondrial Transfer and Immune Function
Mitochondrial transfer between cells has emerged as a key mechanism in regulating immune responses, as discussed by Jonathan Brestoff. His study revealed that adipocyte-derived mitochondria supply macrophages, which play a critical role in metabolic regulation, particularly under high-fat diet conditions. Notably, the transfer of mitochondria from neutrophils to brown fat during cold challenges demonstrates an adaptive mechanism that helps maintain body warmth. This process suggests that mitochondria are not only energy producers but also crucial mediators of immune efficiency.
Extra Follicular B Cell Responses and Autoimmunity
The phenomenon of extra follicular B cell responses, distinct from traditional germinal center reactions, was highlighted in several discussions. These unconventional responses can lead to the generation of memory B cells and antibody production without the typical T cell guidance, particularly following infections and after mRNA vaccinations. Research presented by various speakers pointed to a correlation between extra follicular activation and autoimmune conditions, emphasizing the risks associated with unregulated B cell responses. This increased understanding of B cell dynamics offers valuable insights into the mechanisms underlying autoimmune diseases after infections, such as severe COVID-19.
In May 2024, we attended IMMUNOLOGY2024, the annual meeting of the American Association of Immunologists in Chicago, and recorded daily episodes discussing highlights of the previous 24 hours. Here is the final of five special episodes from the meeting, where Brenda and Jason talk about sessions including the dysfunction of exhaustive T cells enforced by MCT11-mediated lactate metabolism and extrafollicular differentiated B cells, presented by former podcast guest Dr. Frances Lund.
, the annual meeting of the American Association of Immunologists in Chicago, and recorded daily episodes discussing highlights of the previous 24 hours. Here is the final of five special episodes from the meeting, where Brenda and Jason talk about sessions including the dysfunction of exhaustive T cells enforced by MCT11-mediated lactate metabolism and extrafollicular differentiated B cells, presented by former podcast guest Dr. Frances Lund.
