ABSTRACT
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-gamma, 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-gamma, and suggest that they contribute to the pathogenesis of kidney damage in patients with SLE.
Subject(s)
Cell Movement/immunology , Cell Proliferation , Interleukin-17/biosynthesis , Kidney/immunology , Lupus Erythematosus, Systemic/immunology , T-Lymphocyte Subsets/immunology , Adult , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/pathology , Cells, Cultured , Humans , Immunophenotyping , Inflammation Mediators/metabolism , Inflammation Mediators/physiology , Kidney/pathology , Lupus Erythematosus, Systemic/metabolism , Lupus Erythematosus, Systemic/pathology , Middle Aged , T-Lymphocyte Subsets/metabolism , T-Lymphocyte Subsets/pathology , Up-Regulation/immunologyABSTRACT
We discuss a 53-year-old woman with systemic lupus erythematosus who presented with vasculitis, hypocomplementemia and nephritis. Although her serum complement 4 (C4) levels were zero, she had four copies of C4 gene. Renal biopsy revealed membranoproliferative glomerulonephritis and the presence of cryoglobulins, detected by electron microscopy, and significant numbers of T cells in the interstitium. Cryoglobulins were considered responsible for the complete consumption of C4 in the serum the levels of which improved gradually after treatment. T cells in the kidney were found to express CD44 and phosphorylated ezrin/radixin/moiesin which explain why they homed to the kidney inappropriately. The contribution of cryoglobulins and T cells in the expression of kidney pathology is discussed.