Cellular interactions in the pathogenesis of lupus nephritis: the role of T cells and macrophages in the amplification of the inflammatory process in the kidney.
A significant number of T cells and macrophages infiltrate the kidneys of patients with lupus nephritis. Chemotactic factors, especially monocyte chemoattractant factor-1 (MCP-1) and adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), cooperatively facilitate recruitment of mononuclear cells into inflamed tissue. Increased expression of class II MHC molecules and CD40 on renal tubular epithelial cells coupled with upregulation of CD40 ligand (CD40L) and interleukin-2 receptor on infiltrating T cells suggest ongoing cellular immune responses. Recent studies employing knockout mice suggest that the T(H)-1 cytokine interferon-gamma is an important cytokine in amplifying the local immune response of lupus nephritis. Infiltrating mononuclear cells exert their effects on resident renal cells through secretion of soluble factors and/or direct cell to cell contact. These interactions, among others, involve molecules such as CD40/CD40L and adhesion molecules. Studies to better define these molecules are in progress and may provide additional targets for therapeutic intervention. Thus, while autoantibody production and complement activation are the major players in initiating the inflammatory response in lupus nephritis, cellular immune mechanisms mediated through infiltrating mononuclear cells have an important role in its amplification and the progression of renal injury.
Kuroiwa
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T
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Disease, National Institutes of Health, Bethesda, Maryland 20892, USA.
Lee
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EG
D000818:Animals; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D007668:Kidney / Q000166:cytology / Q000473:pathology / Q000503:physiopathology; D008181:Lupus Nephritis / Q000209:etiology* / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology