FoxP3+ CD4+ T cells in systemic autoimmune diseases: the delicate balance between true regulatory T cells and effector Th-17 cells

Abstract

Breakdown of tolerance is a hallmark of autoimmune diseases. Over the past 10 years, there has been increased interest in the role of FoxP3(+) regulatory T cells (T(Regs)) in maintaining peripheral tolerance. Dysfunction of these cells is considered to play a major role in the development of autoimmune diseases. Besides their suppressive function, a fraction of these cells has the capacity to differentiate into IL-17-producing cells (Th-17), a phenomenon associated with autoimmune inflammation. The revealed plasticity of T(Regs), therefore, has obvious implications when designing therapeutic strategies for restoring tolerance in autoimmune diseases using T(Regs). In this review, we discuss development, classification, molecular characterization and mechanisms of suppression by T(Regs). In addition, we describe recent data on their potential conversion into Th-17 cells in human systemic autoimmune diseases. We also outline a new strategy for T(Reg)-based therapy via isolation, expansion and re-infusion of highly pure FoxP3(+) T(Regs) free of contaminating effector T cells.