Interleukin-2 and regulatory T cells in rheumatic diseases

Abstract

Failure of regulatory T (T_reg) cells to properly control immune responses leads invariably to autoimmunity and organ damage. Decreased numbers or impaired function of T_reg cells, especially in the context of inflammation, has been documented in many human autoimmune diseases. Restoration of T_reg cell fitness and/or expansion of their numbers using low-dose natural IL-2, the main cytokine driving T_reg cell survival and function, has demonstrated clinical efficacy in early clinical trials. Genetically modified IL-2 with an extended half-life and increased selectivity for T_reg cells is now in clinical development. Administration of IL-2 combined with therapies targeting other pathways involved in the expression of autoimmune diseases should further enhance its therapeutic potential. Ongoing clinical efforts that capitalize on the early clinical success of IL-2 treatment should bring the use of this cytokine to the forefront of biological treatments for autoimmune diseases.