Regulatory interactions of αβ and γδ T cells in glomerulonephritis

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.