Harnessing regulatory T cells for the therapy of lupus and other autoimmune diseases

Regulatory T cells (Tregs) maintain immunological homeostasis and prevent autoimmunity. The depletion or functional alteration of Tregs may lead to the development of autoimmune diseases. Tregs consist of different subpopulations of cells, of which CD4(+)CD25(+)Foxp3(+) cells are the most well characterized. However, CD8 Tregs also constitute a major cell population that has been shown to play an important role in autoimmune diseases. This review will discuss the role of Tregs in autoimmune diseases in general and specifically in systemic lupus erythematosus (SLE). SLE is a multisystem autoimmune disease characterized by the production of autoantibodies against nuclear components and by the deposition of immune complexes in the kidneys as well as in other organs. Abnormalities in Tregs were reported in SLE patients and in animal models of the disease. Current treatment of SLE is based on immunosuppressive drugs that are nonspecific and may cause adverse effects. Therefore, the development of novel, specific, side effect-free therapeutic means that will induce functional Tregs is a most desirable goal. Our group and others have designed and utilized tolerogenic peptides that ameliorate SLE manifestations in murine models. Here, we demonstrate the role of CD4 and CD8 Tregs, as well as the interaction between the two subsets of cells and the mechanism of action of the tolerogenic peptides. We also discuss their therapeutic potential for the treatment of SLE.