Scientists find optimal method for generating regulatory T cells to treat autoimmune disease
While we normally think of T cells as recognizing invaders, their roles are more complex. For example, some T cells, called regulatory T cells (Tregs) suppress conventional T cells’ immune responses. Because conventional T cells can escape normal controls and drive autoimmune diseases such as rheumatoid arthritis and type 1 diabetes, as well as rejection of transplants, Tregs are increasingly viewed as a way to rein in autoimmune diseases.
Several methods of using a patient’s own T cells to generate large quantities of Treg cells have been developed and are in clinical trials. However, whether all of these methods generate Tregs that effectively control conventional T cells is not clear—each was tested under very different conditions.
Recent research from the laboratory of Salvatore Albani, M.D., Ph.D., adjunct professor and director of SBP’s Translational Research for Infectious and Inflammatory Disease Center, has addressed this question.
“We have created a standardized approach that directly compares methods of generating Tregs. The process is much faster than waiting for clinical results from ongoing trials,” he explained.
“The ultimate outcome of clinical trials using Tregs will depend on many factors since individual diseases are sparked by different triggers in different cell types and tissues. Our goal is to minimize the variation between Tregs so that we can confidently measure treatment benefits.”
In a study published in the Journal of Immunology, Albani’s team shows that taking T cells that are already specified as Tregs and expanding them yields more stable inhibition of conventional T cells than taking a broader group of T cells and inducing them to become Tregs. They also identified a way to check the quality of expanded Tregs—a change in the state (demethylation) of a specific part of the gene for the factor that regulates the Treg gene program (FOXP3) and predicts the stability of Treg activity.
“This work has clear implications for the clinic—patient-derived Tregs made using the expansion method are likely to be more effective than those made with the induction method,” said Albani.
The Journal of Immunology paper is available online here.