Regulatory T Cells: Differentiation and Function

Abstract

The immune system of vertebrate animals has evolved to mount an effective defense against a diverse set of pathogens while minimizing transient or lasting impairment in tissue function that could result from the inflammation caused by immune responses to infectious agents. In addition, misguided immune responses to "self" and dietary antigens, as well as to commensal microorganisms, can lead to a variety of inflammatory disorders, including autoimmunity, metabolic syndrome, allergies, and cancer. Regulatory T cells expressing the X chromosome-linked transcription factor Foxp3 suppress inflammatory responses in diverse biological settings and serve as a vital mechanism of negative regulation of immune-mediated inflammation. Cancer Immunol Res; 4(9); 721-5. ©2016 AACR.

Fig. 1

Regulatory T cells function in multiple biological contexts, including autoimmunity, cancer, acute and chronic infections, host-commensal interactions and inflammation at barrier sites, allergy, pregnancy, tissue repair, metabolic sterile inflammation, and allo-transplantation.

Fig. 2

Treg cells control inflammation and all known types of the immune response by employing diverse mechanisms of suppression including, but not limited to: 1) production of immunomodulatory cytokines such as IL10 and TGFβ capable of suppressing pro-inflammatory responses of T cells, NK cells, B cells, dendritic cells (DC), and macrophages (Mph); 2) enzymatic activity of CD39 and CD73 ecto-enzymes highly expressed on the Treg cell surface, which enable conversion of extracellular ATP (serving as a pro-inflammatory mediator) to AMP and to adenosine, which then acts through adenosine receptors expressed by innate and adaptive immune cells (T cells, B cells, Mph, and DCs) and other cell types to suppress inflammatory responses; 3) consumption of IL2 by Treg cells, due to high expression of CD25, the high-affinity subunit of the IL2 receptor, restrains responses of CD8 T cells and likely NK cells; and 4) high expression of CTLA-4 enables downregulation of costimulatory molecules CD80 and CD86 expression on DCs (4, 28). Suppressor function of Treg cells is potentiated by signals through TCR and IL2 receptor (30, 31)