3D illustration of a T cell. Image credit: Blausen Medical (CC BY 3.0)
Specialized cells in the immune system known as T cells protect the body from infection by destroying disease-causing microbes, such as bacteria or viruses. T cells use proteins on their surface called receptors to stick to infectious microbes and remove them from the body. Some newly developed T-cells, however, contain receptors that recognize and bind to cells that belong in the body. If these faulty T cells are released, they can attack healthy tissues and cause an autoimmune disease.
After a new T cell is developed, it gets carried to a gland in the chest known as the thymus. Cells in the thymus called mTECs screen T cells for receptors that may bind to the body’s tissues. mTECs do this by presenting T cells with proteins that are commonly found on the surface of healthy cells in the body. If a T cell recognizes any of these ‘tissue specific proteins’, it is destroyed or given a new role in the body. Some faulty T cells, however, still manage to evade detection. One way to uncover why this might happen is to investigate how mTECs develop. Previous work showed that mTECs transition through various stages before reaching their final form. However, the order in which these events occur remained unclear.
To gain a better understanding of these developmental steps, Wells, Miller et al. extracted mTECs from the thymus of mice and analyzed the genetic make-up of individual cells. This uncovered a missing link in mTEC development: a new type of cell that is the immediate predecessor of the final mTEC. These ‘predecessor’ cells were actively growing, highlighting that mTECs can be constantly generated in the body. By probing the genes that generate tissue-specific proteins in mTECs, Wells, Miller et al. revealed that these proteins were only produced for short periods and in the late stages of mTEC development.
These findings contribute to our understanding of how mTECs develop to screen T cells. Mapping these developmental stages will make it easier to identify when faulty T cells are able to evade mTECs. This will lead to earlier detection of autoimmune diseases which could result in better treatments.
