Regulatory T cells and inhibitory cytokines in autoimmunity

Foxp3(+) regulatory T cells (T-regs) contribute significantly to the maintenance of peripheral tolerance, but they ultimately fail in autoimmune diseases. The events that lead to T-reg failure in controlling autoreactive effector T cells (T-effs,) 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 T,g function; secondly, the issue of T-reg plasticity; thirdly, the possible resistance of autoimmune T cells to T-reg-mediated control; and fourthly, T-reg-associated inhibitory cytokines TGF beta, IL-10 and IL-35 in facilitating T-reg suppressive activity and promoting T-reg generation. These recent advances place a large emphasis on the local tissue specific inflammatory environment as it relates to T-reg function and disease development.