Regulatory T cells in systemic lupus erythematosus: past, present and future

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.

Figure 1

T-cell/dendritic cell interactions in health and in systemic lupus erythematosus. Regulatory T cells (Tregs) (red) and effector T cells, shown as potentially pathogenic anti-self T cells (blue), can affect the maturation of immature dendritic cells (DCs) to immunogenic or tolerogenic antigen-presenting cells. Transforming growth factor beta (TGFβ) and IL-10 produced by Tregs promote tolerogenic DCs, and IFNγ or IL-17 produced by effector T cells promotes immunogenic DCs. Toll-like receptor (TLR) 7 and TLR9 stimulation by apoptotic bodies in systemic lupus erythematosus (SLE) results in type 1 interferon production, which promotes immunogenic DCs that activate potentially pathogenic self-reactive T cells. The feedback loop shown sustains immunogenic DCs and, secondarily, results in decreased Tregs.