T cells as therapeutic targets in SLE

Abstract

Recent advances have shed light on the biochemical and molecular aberrations that lead to the characteristic cytokine production pattern and altered behavior of T cells in systemic lupus erythematosus (SLE). This article reviews how this knowledge helps explain the nature of the SLE T cell, identifies therapeutic targets that deserve further development, and identifies biomarkers of disease activity. T cells contribute to the initiation and perpetuation of autoimmunity in systemic lupus erythematosus (SLE), and seem to be directly involved in the development of related organ pathology. Defects associated with CD8+ and T-regulatory (TREG) cell function manifest in parallel with the expanded CD3+CD4−CD8− T cell lineage. The cytokine expression pattern is uniquely characterized by decreased expression of interleukin (IL)-2 and increased production of IL-17 and related cytokines. Therapeutic approaches that limit the cognate interaction between T cells and B cells, prevent inappropriate tissue homing and restore TREG cell function and the normal cytokine milieu have been entertained. Biochemical characterization of SLE T cells has revealed distinct early and late signaling aberrations, and has enabled the identification of novel molecular targets that can be corrected with small molecules, and biomarkers that may foretell disease activity and predict organ damage.