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Rosenkranz, AR; Knight, S; Sethi, S; Alexander, SI; Cotran, RS; Mayadas, TN.
Regulatory interactions of alphabeta and gammadelta T cells in glomerulonephritis.
Kidney Int. 2000; 58(3):1055-1066 Doi: 10.1046/j.1523-1755.2000.00263.x [OPEN ACCESS]
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Leading authors Med Uni Graz: Rosenkranz Alexander
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Abstract:: Background. Several lines of evidence suggest that cellular immune mechanisms contribute to glomerulonephritis. Method's. The roles of alpha beta and gamma delta T cells in the pathogenesis of glomerulonephritis were investigated in a model of nephrotoxic nephritis in mice deficient in either T-cell population [T-cell receptor (TCR)beta and TCR delta knockout mice]. The model, induced by the injection of rabbit anti-mouse glomerular basement membrane antibody, is characterized by the development of proteinuria and glomerular damage over a 21-day observation period in wild-type mice. Results. Mice deficient in either alpha beta or gamma delta T cells developed minimal proteinuria and glomerular lesions and had a significant reduction in macrophage accumulation compared with wild-type mice. In gamma delta T-cel-deficient mice, circulating levels and glomerular deposition of autologous IgG were comparable to wild-type levels, while alpha beta T-cell-deficient mice had no autologous IgG production. Autologous antibody production was not required for the development of glomerulonephritis since mice that lack IgG and B cells (mu-chain-/-) developed similar proteinuria to that observed in wild-type mice. Conclusions. These studies suggest a proinflammatory role for both alpha beta and gamma delta T cells in glomerular injury, independent of the humoral response. This is the first demonstration, to our knowledge, that both T-cell subsets contribute to the progression of a disease, and it suggests that complex regulatory interactions between alpha beta and gamma delta T cells play a role in glomerular injury.
Find related publications in this database (using NLM MeSH Indexing): Animals -; Antibodies -; B-Lymphocytes - immunology; Basement Membrane - immunology; CD8-Positive T-Lymphocytes - immunology; Complement System Proteins - analysis; Gene Expression - immunology; Glomerulonephritis - immunology Glomerulonephritis - metabolism Glomerulonephritis - pathology; Immunity, Cellular - immunology; Immunoglobulin G - immunology Immunoglobulin G - metabolism; Kidney Glomerulus - immunology Kidney Glomerulus - pathology; Macrophages - immunology; Mice -; Mice, Inbred C57BL -; Mice, Transgenic -; Proteinuria - immunology Proteinuria - metabolism Proteinuria - pathology; RNA, Messenger - analysis; Receptors, Antigen, T-Cell, alpha-beta - genetics Receptors, Antigen, T-Cell, alpha-beta - metabolism; Receptors, Antigen, T-Cell, gamma-delta - genetics Receptors, Antigen, T-Cell, gamma-delta - metabolism
Find related publications in this database (Keywords): T cell receptor; transgenic mice; cellular immunity; macrophages; inflammation