Regulatory T cells and inhibitory cytokines in autoimmunity

Foxp3+ regulatory T cells (Tregs) contribute significantly to the maintenance of peripheral tolerance, but they ultimately fail in autoimmune diseases. The events that lead to Treg failure in controlling autoreactive effector T cells (Teffs) during autoimmunity are not completely understood. In this review, we discuss possible mechanisms for this subversion as they relate to type 1 diabetes (T1D) and multiple sclerosis (MS). Recent studies emphasize firstly, the role of inflammatory cytokines, such as IL-6, in inhibiting or subverting Treg function; secondly, the issue of Treg plasticity; thirdly, the possible resistance of autoimmune T cells to Treg-mediated control; and fourthly, Treg-associated inhibitory cytokines TGFβ, IL-10 and IL-35 in facilitating Treg suppressive activity and promoting Treg generation. These recent advances place a large emphasis on the local tissue specific inflammatory environment as it relates to Treg function and disease development.