The new ‘GLed’ tool, unique in its reversibility, allows the functional state of T cells to be observed for the first time, representing a crucial advance in personalizing treatments in immunotherapy, transplants, and autoimmune diseases
Researchers at the University of Granada and Mount Sinai Hospital in New York have developed a luminescent probe, called ‘GLed’, capable of measuring the activity of the immune system in real time and with unprecedented accuracy. This innovative tool allows the level of activity of human T cells (responsible for the immune response) to be visualized, enabling medical professionals to predict patient response, adjust immunosuppressant doses, and personalize treatments for cancer or organ transplants, marking the beginning of a new era in precision medicine. The results of this work, which has been featured on the cover of the interdisciplinary scientific journal Advanced Science, open up new possibilities for functional monitoring and the development of individualized therapies.
A “molecular beacon” that lights up in real time
This breakthrough, the result of the project ‘PoTraSens – Detection of post-translational modifications in T cells. Towards new applications in immunology (reference PID2023-148243OBI00)’, funded by the Spanish Research Agency (National R&D&I Plan, in its Challenges modality), addresses one of the great challenges of modern immunology: the lack of methods to functionally and directly quantify the actual degree of immunosuppression or the strength of a patient’s immune response.
The ‘GLed’ probe acts as a “molecular beacon” that lights up when it detects the presence of glutathione within cells, an essential antioxidant molecule that is a
key indicator of cellular activity, especially in stressful situations. Its design is unique because of its high sensitivity, immediate response, and, above all, its reversibility. This means that it not only turns on, but also turns off dynamically, allowing scientists to monitor changes in immune cell activity live and in ultra-fast detail, something that was impossible with previous techniques.
The study’s researchers used the ‘GLed’ probe to decipher how glutathione production is regulated when T cells are activated. The results revealed that the GCL enzyme is solely responsible for generating new glutathione in activated human T cells and also confirmed that if GCL activity is blocked, T cells cannot perform their critical functions, such as multiplying to attack a threat or releasing inflammatory molecules.
Measuring the real effect of immunosuppressive drugs
One of the most immediate applications tested in the study was measuring the effect of common immunosuppressive drugs such as prednisone and tacrolimus, used to prevent rejection in organ transplants. The ‘GLed’ probe revealed that all these drugs reduce the activity of the GCL enzyme, and that this decrease is parallel to the degree of cellular immunosuppression. For the first time, the level of immune system suppression can be measured directly and functionally, allowing doses to be adjusted individually for each patient.
The ‘GLed’ probe is a pioneering tool for basic science, allowing the role of glutathione in immunological, inflammatory, and tumor processes to be studied with unprecedented resolution. In the long term, its implementation in clinical practice could revolutionize the functional monitoring of patients and the development of new personalized therapies for cancer, autoimmune diseases, and transplants.
This research is the result of an international multidisciplinary collaboration led by the Singular Nanoscopy-UGR Laboratory at the University of Granada and the groups of Dr. Francisco Fueyo-González and Dr. Miguel Fribourg at the Icahn School of Medicine at Mount Sinai Hospital in New York. The Granada team is made up of Carmen Salto Girón, José M. Paredes, Ángel Orte, and Juan Antonio González Vera, while the New York team includes researchers Mehek Ningoo and Laura Espinar Barranco, with contributions from Rafael Salto, from the Department of Biochemistry and Molecular Biology II at the University of Granada, and Rosario Herranz, from the Institute of Medical Chemistry at the Spanish National Research Council (CSIC).