Double negative (DN) T cells are expanded in patients with systemic lupus erythematosus (SLE) and stimulate autoantibody production as efficiently as CD4+ T cells. In this study, we demonstrate that DN T cells from patients with SLE produce significant amounts of IL-17 and IFN-γ, and expand when stimulated in vitro with an anti-CD3 Ab in the presence of accessory cells. Furthermore, IL-17+ and DN T cells are found in kidney biopsies of patients with lupus nephritis. Our findings establish that DN T cells produce the inflammatory cytokines IL-17 and IFN-γ, and suggest that they contribute to the pathogenesis of kidney damage in patients with SLE.

Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects women and presents with manifestations derived from the involvement of multiple organs including the kidneys, joints, nervous system, and hematopoietic organs. Immune system aberrations, as well as heritable, hormonal, and environmental factors interplay in the expression of organ damage. Recent contributions from different fields have developed our understanding of SLE and reshaped current pathogenic models. Here, we review novel information that deals with 1) genes associated with disease expression, 2) immune cell molecular abnormalities that lead to autoimmune pathology, 3) the role of hormones and sex chromosomes in the development of disease, 4) environmental and epigenetic factors thought to contribute to the expression of SLE. Finally, we emphasize molecular defects intimately associated with the disease process of SLE that represent ideal therapeutic targets and disease biomarkers.

T cells that express IL-17 infiltrate the kidneys of patients with systemic lupus erythematosus. A significant proportion of these cells are CD3+CD4−CD8− double-negative T cells. In this study, we show that double-negative T cells from MRL/lpr mice express high amounts of IL-17 and that as disease progressively worsens, the expression of IL-17 and of IL-23 receptor in lymphocytes from these mice increases. Lymph node cells from lupus-prone mice, but not control mice, treated in vitro with IL-23 induce nephritis when transferred to non-autoimmune, lymphocyte-deficient Rag-1−/− mice. Kidney specimens from these recipient mice show significant Ig and complement deposition. The data indicate that an aberrantly active IL-23/IL-17 axis contributes to the development of nephritis in lupus-prone mice.