[HTML][HTML] Regulatory interactions of αβ and γλ T cells in glomerulonephritis

AR Rosenkranz, S Knight, S Sethi, SI Alexander… - Kidney international, 2000 - Elsevier
AR Rosenkranz, S Knight, S Sethi, SI Alexander, RS Cotran, TN Mayadas
Kidney international, 2000Elsevier
Regulatory interactions of αβ and γλ T cells in glomerulonephritis. Background Several lines
of evidence suggest that cellular immune mechanisms contribute to glomerulonephritis.
Methods The roles of αβ and γλ 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) β and TCRλ knockout mice]. The model, induced by the injection of
rabbit anti-mouse glomerular basement membrane antibody, is characterized by the …
Regulatory interactions of αβ and γλ T cells in glomerulonephritis.
Background
Several lines of evidence suggest that cellular immune mechanisms contribute to glomerulonephritis.
Methods
The roles of αβ and γλ 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)β and TCRλ 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 αβ or γλ T cells developed minimal proteinuria and glomerular lesions and had a significant reduction in macrophage accumulation compared with wild-type mice. In γλ T-cell–deficient mice, circulating levels and glomerular deposition of autologous IgG were comparable to wild-type levels, while αβ 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 (μ-chain-/-) developed similar proteinuria to that observed in wild-type mice.
Conclusions
These studies suggest a proinflammatory role for both αβ and γλ 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 αβ and γλ T cells play a role in glomerular injury.
Elsevier