Regulatory T cells and human disease

Abstract

The main function of our immune system is to protect us from invading pathogens and microorganisms by destroying infected cells, while minimizing collateral damage to tissues. In order to maintain this balance between immunity and tolerance, current understanding of the immune system attributes a major role to regulatory T cells (Tregs) in controlling both immunity and tolerance. Various subsets of Tregs have been identified based on their expression of cell surface markers, production of cytokines, and mechanisms of action. In brief, naturally occurring thymic-derived CD4+CD25+ Tregs are characterized by constitutive expression of the transcription factor FOXP3, while antigen-induced or adaptive Tregs are mainly identified by expression of immunosuppressive cytokines (interleukin-10 (IL-10) and/or transforming growth factor-beta (TGF-beta)). While Tregs in normal conditions regulate ongoing immune responses and prevent autoimmunity, imbalanced function or number of these Tregs, either enhanced or decreased, might lead, respectively, to decreased immunity (e.g., with tumor development or infections) or autoimmunity (e.g., multiple sclerosis). This review will discuss recent research towards a better understanding of the biology of Tregs, their interaction with other immune effector cells, such as dendritic cells, and possible interventions in human disease.

Figure 1

Possible mechanisms of suppression by regulatory T cells (Tregs). Tregs mediate their suppressive action by direct cell-cell contact mediated by CTLA-4 on both effector T cells as well as antigen-presenting cells (APCs), such as dendritic cells (DCs). Production of immunosuppressive cytokines, such as IL-10 and TGF-β, suppresses DC maturation, making DCs tolerogenic. Moreover, Tregs can kill effector T cells by expression of perforin and granzyme A. The figure also indicates therapeutic action of the anti-CTLA-4 antibody.