Regulatory T cells: Master thieves of the immune system

Abstract

Treg cells are the immune system's in-house combatants against pathological immune activation. Because they are vital to maintenance of peripheral tolerance, it is important to understand how they perform their functions. To this end, various mechanisms have been proposed for Treg-mediated immune inhibition. A major group of mechanisms picture Treg cells as skilled thieves stealing a plethora of molecules that would otherwise promote immune effector functions. This suggests that several million years of evolution have endowed Treg cells with efficient ways to deprive immune effectors of activating stimuli to prevent immunopathology for survival of the host. Although we are still long way from deciphering their complete set of tricks, this review will focus on the types of "crimes" committed by these master thieves in both secondary lymphoid organs and non-lymphoid tissue.

Keywords: Foxp3; Suppressor cytokines; Suppressor mechanisms; Treg cells.

Figure 1.

Two fundamentally different suppressor modes characterize Treg suppressor mechanisms. In the “active” mode, Treg secrete immunoinhibitory molecules that exert their effects on other cell types. In contrast, in the “counteractive” mode Treg are actively engaged in removing vital components from other cells types including antigen, costimulatory molecules, cytokines, and inflammatory signals thereby decreasing the activation of T effector cells.

Figure 2.

The “stealing” of pMHCII complexes from DC surfaces functions most effectively under limiting antigen conditions (left panel). The process can be helped by simultaneous removal of costimulatory molecules. In contrast, in the presence of high concentrations of antigen, the theft of pMHCII complexes is unlikely to be an effective suppressive mechanisms (right panel). More active mechanisms such as the secretion of inhibitory cytokines must be called into action.