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Revolutionary T cells: The body prepares itself for infections at an early stage!
Researchers from TUM and Helmholtz Munich show how the body mobilizes T cells during early infections and influences their function.
Revolutionary T cells: The body prepares itself for infections at an early stage!
Researchers of the Technical University of Munich (TUM) and Helmholtz Munich recently discovered in a comprehensive study that the human body prepares itself for potentially serious disease progression even at the beginning of uncomplicated infections. This finding could have far-reaching implications for the treatment of diseases.
Traditionally, it was considered certain that special T cells, which are responsible for fighting pathogens, are only produced in chronic and severe infections and in tumors. But the new research shows that even in the early stages of moderate illness, the body primes T cell subtypes that are vulnerable to exhaustion. T cells are crucial for controlling the immune response and fighting pathogens. In the study, Dietmar Zehn, professor of animal physiology and immunology at TUM and last author, explained that some of these subtypes reduce or even stop their activity as the disease progresses. At first glance, this can be seen as a protective function as it prevents damage caused by long-term illnesses.
T cell exhaustion and its causes
Nevertheless, T cell exhaustion also poses significant risks, especially in the treatment of serious diseases such as cancer. In this context, the research team led by Martin Väth at the Julius Maximilian University of Würzburg
Optimizing cellular metabolism could increase the longevity and functionality of T cells. Particularly interesting are the findings that overexpression of a mitochondrial transporter crucial for the production of adenosine triphosphate (ATP) could reduce exhaustion. Current therapies such as CAR-T cells have already shown success in leukemia and lymphoma, but have had limited success in solid tumors, which is also linked to T cell exhaustion.
Research and future prospects
A new genetic model has been developed to analyze the connection between mitochondrial metabolism and loss of T cell function. In these experiments, the mitochondrial phosphate transporter (SLC25A3) was switched off, which led to the paralysis of cellular respiration and activated alternative metabolic pathways. This adaptation causes an increased formation of oxygen radicals, which inhibits the degradation of the transcription factor HIF-1-alpha. The accumulation of HIF-1-alpha in the cell nucleus in turn accelerates T cell exhaustion.
The discovery of these new regulatory mechanisms between cellular respiration and T cell function is called “metabolic checkpoint” and offers new approaches for the treatment of diseases. Future research should highlight the influence of mitochondrial cellular respiration on the epigenetic programming of T cells, also taking into account environmental conditions such as nutrient content and oxygen saturation. This work was largely carried out in Martin Väth's laboratory and was financially supported by the German Research Foundation (DFG).
Overall, the results of the entire research efforts of TUM and the University of Würzburg are an important step in understanding the immune system. These findings could not only be important for the development of new diagnostic procedures and therapies, but also fundamentally change our understanding of how the body reacts to infections.