The body has an army of millions of immune cells. These cells contain receptors generated through random genetic rearrangements, a clever strategy to keep them ready to fight unfamiliar viruses and bacteria. However, this diverse pool leaves many questions about which ones are active in specific diseases. Now, a study from researchers at The Scripps Research Institute (TSRI) identifies a previously unknown type of immune cell; the newly discovered cells resemble conventional T cells, yet are biased toward becoming T regulatory cells (Tregs), which protect the body from autoimmune disease. The team state that the discovery opens new avenues in the effort to develop novel therapies for autoimmune diseases such as type 1 diabetes. The study is published in the journal Proceedings of the National Academy of Sciences.
Previous studies show that one disease still puzzling global medical community is Type 1 diabetes, in which immune cells mistakenly attack insulin-producing cells in the pancreas. It is known that Tregs should be able control this autoimmune response, deflecting the attack, therefore current clinical trials are focusing on increasing the numbers of Treg cells and finding ways to make them enter the pancreas. The current study investigates the development and function of natural-arising T regulatory (nTreg) cells and in doing-so, identifies a previously unknown T-cell subset that functions as a peripheral precursor of nTreg cells.
The current study isolates an individual Treg from a mouse model of type 1 diabetes and inserts its nucleus, containing the unique genetic immune receptor information, into a mouse egg cell that has its own nucleus removed. Results show that by using this cloning method, a mouse model can be developed that produces only the original Treg, allowing the study of its origins and functions for the first time. Data findings show that the Treg originated in a lymphoid organ called the thymus, making it a ‘naturally’ arising Treg, called an nTreg.
Results show that the mice could only make one type of T cells, yet the lab observed a second type of T cell in the thymus and spleen. Data findings show that this particular T cell type exists in two functional states, an amazing discovery. After repeating their experiment several times, the group determined that the two T cell types, while genetically identical, looked different because one of them could switch on a gene called FoxP3. The researchers state that an nTreg with inactive FoxP3 (named a pre-nTreg) looked like any other conventional T cell, however, when activated the pre-nTreg became an nTreg.
The team surmise that their findings indicate that pre-nTregs may be activated in response to many kinds of immune challenges, such as autoimmune diseases, cancer and infections. They go on to add that one of the big questions now is whether a future therapy could push more pre-nTregs to activate and control diseases such as diabetes. For the future, the researchers state that they also plan to such develop markers to identify different Treg and pre-Treg types.