IL-2 immunotherapy for targeting regulatory T cells in autoimmunity

FOXP3(+) regulatory T cells (T(reg)) are indispensable for immune homoeostasis and for the prevention of autoimmune diseases. Interleukin-2 (IL-2) signalling is critical in all aspects of T(reg) biology. Consequences of defective IL-2 signalling are insufficient numbers or dysfunction of T(reg) and hence autoimmune disorders in human and mouse. The restoration and maintenance of immune homoeostasis remain central therapeutic aims in the field of autoimmunity. Historically, broadly immunosuppressive drugs with serious side-effects have been used for the treatment of autoimmune diseases or prevention of organ-transplant rejection. More recently, ex vivo expanded or in vivo stimulated T(reg) have been shown to induce effective tolerance in clinical trials supporting the clinical benefit of targeting natural immunosuppressive mechanisms. Given the central role of exogenous IL-2 in T(reg) homoeostasis, a new and promising focus in drug development are IL-2-based approaches for in vivo targeted expansion of T(reg) or for enhancement of their suppressive activity. In this review, we summarise the role of IL-2 in T(reg) biology and consequences of dysfunctional IL-2 signalling pathways. We then examine evidence of efficacy of IL-2-based biological drugs targeting T(reg) with specific focus on therapeutic candidates in clinical trials and discuss their limitations.