A recent study in Nature Immunology by Dr. Alfred Singer and colleagues demonstrate how T cells develop through a complex process known as agonist signaling. This novel study helps establish foundational knowledge of T cell development and has implications beyond the lab bench.
Immune cells are generated to fight infection and disease throughout our body. A critical population of immune cells is T cells, which can further be divided into subtypes based on function. Different subtypes of T cells have a myriad of functions, including activation of the immune system. T cells were the population of interest in the study due to their requirement for strong immunity and necessary response to infection. However, T cells have a complex maturation process in which they develop into different T cell subtypes making it difficult to understand their biology.
T cells mature in the thymus through a process known as thymic selection. Thymic selection is a screening process for T cells. Selection occurs to confirm the body does not reject its own cells. When thymic selection is dysregulated, an individual can have an autoimmune disorder in which the cells in the immune system do not recognize itself and will attack beneficial cells in the body. T cells with autoreactive T cell receptors (TCRs) have an affinity for self-ligands, or molecules released by the same cell that possesses the TCR. The binding of self-ligands to the TRC on the same cell creates agonist signaling. These agonist signals are responsible for further thymocyte selection in which the cells undergo processes that generate specific T cell subtypes. However, the role agonist signaling plays in T cell development is unclear in the field. Further analysis on how T cell development occurs will change therapeutic approaches to autoimmune disorders.
Singer and colleagues, at the National Institute of Health (NIH), found that agonist signaling and time of signaling is necessary for the development of T cells. It was determined that different T cell subtypes required agonist signaling to occur later on in the developmental process. Additionally, the disruption of agonist-signaling was found to lead to the development of T cells that suppress the immune response, known as regulatory T cells (Tregs). Alternatively, persistent agonist signaling leads to T cells responsible for immune stimulation, referred to as effector T cells (Teff cells). These findings have major therapeutic implications due to their function in the immune system.
Singer and colleagues have defined the general mechanism of T cell development and provided evidence for agonist signaling in the generation of specific T cell subtypes. This foundational work in establishing how T cells can further develop through agonist signaling expands our current knowledge of T cell biology. More importantly, the implications of understanding T cell development can improve therapeutic interventions and help us better treat patients with a wide range of diseases, including autoimmune disorders.
Study, Nature Immunology, Alfred Singer, Tregs, Teff cells, NIH, T cells, Maturation Process
