Our immune systems develop to recognize what is foreign within our bodies. As immune cells are generated in the bone marrow and mature in other locations, they undergo processes that instruct which cells and tissues are ‘self’ vs ‘non-self’. While all immune cells maintain an innate ability to discern what is foreign and what is not, this function is especially important for cells that play a larger role in immunity. T cells are generated in the thymus and are produced to recognize and target pathogens. As these cells develop, they are trained to recognize ‘non-self’ markers and eliminate them. This pathogen recognition allows for efficient, orchestrated immune response as T cells provide surveillance of ‘non-self’ biomaterial.
While our bodies try to constantly maintain healthy immunity, it can misinterpret which is ‘self’ and ‘non-self’. Autoimmune disorders occur when the body’s immune system targets the individuals’ own healthy tissues and organs. Consequently, this can lead to various symptoms and cause serious illness. Autoimmunity can be caused through several factors including genetic variables, environmental triggers, and direct dysfunction of the immune system. Currently, there are over 80 autoimmune diseases with no cure. Symptoms may include fatigue, swelling, skin rashes, fever, organ dysfunction, and others. Although there is no cure for any particular autoimmune disorder, many treatments focus on relieving symptoms. Physicians may prescribe different medications, immunotherapies, and even surgery to help reduce pain and avoid further complications. Due to the lack of efficient treatment for autoimmune disorders, many scientists investigate the underlying cause of autoimmunity and how we can better generate treatments.
A recent article in Science, by Dr. Peter Savage and others, demonstrates that a T cell subset prevents immune cells from attacking healthy cells and tissues. This discovery helps better inform scientists of how the immune system regulates itself and prevents autoimmune disease from occurring. Savage is Professor in the Department of Pathology at the University of Chicago, where he serves on several committees for immunology and cancer biology. His research interests focus on immune cell tolerance, cancer immunology, and T cell biology. More specifically, his work investigates the development and functions of a T cell subset, known as T regulatory cells (Tregs).
The function of Tregs has been known to survey the body and mediate immune response. Particularly, these cells have been found to help prevent chronic inflammation and bring the body back to normal homeostatic levels. However, it was not clear how Tregs know when to intervene and prevent autoimmune disorders. Researchers employed various laboratory methods to investigate Tregs role in autoimmunity.
To understand the importance of Tregs, Savage and his group depleted Tregs in mice and introduced different bacteria that could initiate an immune response. What scientists discovered was that the depletion of Tregs impaired immune cell response to the bacterial infection. More specifically, conventional T cells were unable to prevent autoimmunity without Tregs present. Researchers also report the interaction between Tregs and other T cell subsets, which demonstrates how Tregs mitigate immune response to reduce risk for autoimmunity. Savage and his team explain that there needs to be a matched number of Tregs to other T cells to avoid autoimmunity. This work helps identify the critical importance of Tregs in autoimmune disorders after infection. Overall, Savage and others for the first time demonstrate the immune-modulated mechanism that drives autoimmunity during infection. This work has major implications to not only basic T cell biology, but to the clinic. Their discovery has the potential to enhance autoimmune treatment and alleviate patient symptoms.
