How regulatory T cells work

Abstract

How regulatory T cells work Dario A. A. Vignali, Lauren W. Collison, and Creg J. Workman Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Abstract Regulatory T (Treg) cells are essential for maintaining peripheral tolerance, preventing autoimmune diseases and limiting chronic inflammatory diseases. However, they also limit beneficial responses by suppressing sterilizing immunity and limiting anti-tumour immunity. Given that Treg cells can have both beneficial and deleterious effects, there is considerable interest in determining their mechanisms of action. In this Review, we discuss the basic mechanisms used by Treg cells to mediate suppression, and discuss whether one or many of these mechanisms are likely to be crucial for Treg- cell function. In addition, we present the hypothesis that effector T cells may not be ‘innocent’ parties in this suppressive process and might in fact potentiate Treg-cell function. Several sophisticated regulatory mechanisms are used to maintain immune homeostasis, prevent autoimmunity and moderate inflammation induced by pathogens and environmental insults. Chief amongst these are regulatory T (Treg) cells that are now widely regarded as the primary mediators of peripheral tolerance. Although Treg cells play a pivotal role in preventing autoimmune diseases, such as type 1 diabetes1,2, and limiting chronic inflammatory diseases, such as asthma and inflammatory bowel disease (IBD)3,4, they also block beneficial responses by preventing sterilizing immunity to certain pathogens5,6 and limiting anti-tumour immunity7. A seminal advance in the analysis of Treg cells came with the identification of a key transcription factor, forkhead box P3 (FOXP3), that is required for their development, maintenance and function8,9. Mice and patients that lack FOXP3 develop a profound autoimmune-like lymphoproliferative disease that graphically emphasizes the importance of Treg cells in maintaining peripheral tolerance1

Key Biomarkers

Symptom Clusters