How the Immune System Learns to Distinguish Between Self and Non-Self

June 16, 2022

T cells are an important immune cell. They develop in the thymus and then circulate throughout the body to aid in its defense. Critical T cell training happens within the thymus to help make T cells tolerant to self, including a process known as negative selection. During negative selection, T cells that identify the body’s own tissues as foreign are eliminated. This ensures that self-reactive T cells that could contribute to autoimmunity do not survive. In a study titled Thymic epithelial cells co-opt lineage-defining transcription factors to eliminate autoreactive T cells, published in Cell, scientists discovered insight into how this process happens.

This study used mouse models to investigate the process of T cell training within the thymus by focusing on cells known as medulla thymic epithelial cells, also known as mTECs. These cells are the ones that help show T cells self-antigens, which are proteins from the body’s own cells.

For a long time, scientists believed that a protein called AIRE played the primary role in assisting mTECs in presenting self-antigens for T cell selection. However, this study revealed additional factors contributing to the development of distinct types of mTECs. These mTECs appear similar to those found in cells from other parts of the body, leading the researchers to call them ‘mimetic cells’. 

This is a significant finding as it provides further insights into how T cells can be trained to recognize and tolerate the diverse array of body cells they encounter after leaving the thymus. These mimetic cells look similar to those body cells, so T cells can be trained to tolerate them prior to leaving the thymus. More research is needed to understand how this process may be altered in individuals with autoimmunity and if it can be targeted for future treatments. 

Citation for report:

Michelson, D. A., Hase, K., Kaisho, T., Benoist, C., & Mathis, D. (2022). Thymic epithelial cells co-opt lineage-defining transcription factors to eliminate autoreactive T cells. Cell, 185(14), 2542–2558.e18. https://doi.org/10.1016/j.cell.2022.05.018.