Abstract
Regulatory/suppressor T cells (Tregs) maintain immunologic homeo-stasis and prevent autoimmunity. In this article, past studies and recent studies of Tregs in mouse models for lupus and of human systemic lupus erythematosus are reviewed concentrating on CD4+CD25+Foxp3+ Tregs. These cells consist of thymus-derived, natural Tregs and peripherally induced Tregs that are similar phenotypically and functionally. These Tregs are decreased in young lupus-prone mice, but are present in normal numbers in mice with established disease. In humans, most workers report CD4+Tregs are decreased in subjects with active systemic lupus erythematosus, but the cells increase with treatment and clinical improvement. The role of immunogenic and tolerogenic dendritic cells in controlling Tregs is discussed, along with new strategies to normalize Treg function in systemic lupus erythematosus.
Highlights
Systemic lupus erythematosus (SLE) is a disorder of immune regulation characterized by the breakdown of tolerance to self-nuclear, cytoplasmic and cell surface molecules and by the production of autoantibodies to these elements
Polyclonal iTregs induced by stimulating T cells with anti-CD3/CD28-coated beads with IL-2 and TGFβ have been recently found to have protective effects in this model and other mouse models of autoimmune disease [28]; in a collaboration with Antonio La Cava and Bevra Hahn at UCLA, we have found these polyclonal iTregs have protective effects in the BWF1 model
Transforming growth factor beta (TGFβ) and IL-10 produced by Tregs promote tolerogenic dendritic cells (DCs), and IFNγ or IL-17 produced by effector T cells promotes immunogenic DCs
Summary
Systemic lupus erythematosus (SLE) is a disorder of immune regulation characterized by the breakdown of tolerance to self-nuclear, cytoplasmic and cell surface molecules and by the production of autoantibodies to these elements. Datta’s group reported that low-dose peptide subcutaneous immunization induces SNF1 mice to develop Foxp3+CD4+ and Foxp3+CD8+ Tregs that produce TGFβ, resulting in a delay of glomerulonephritis and prolonged survival [32]. A third group reported that the percentage of CD4+CD25high cells in SLE in patients with active disease was normal, the relative number of these Tregs was decreased because of a greater expansion of effector T cells [59].
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