Th2 responses induce humorally mediated injury in experimental anti-glomerular basement membrane glomerulonephritis.

Acute autologous phase anti-glomerular basement membrane glomerulonephritis was compared in Th1-prone (C57BL/6) and Th2-prone (BALB/c) mice. Sensitized BALB/c mice, given a subnephritogenic intravenous dose of anti-mouse glomerular basement membrane globulin, developed acute glomerulonephritis characterized by marked proteinuria and glomerular deposition of mouse immunoglobulin and complement. A significant glomerular neutrophil influx was observed, but few T cells and macrophages were present. C57BL/6 mice, given the same dose of disease-inducing globulin, also developed acute glomerulonephritis, although their proteinuria was significantly less. Glomerular deposition of mouse immunoglobulin and complement and the influx of neutrophils were also significantly less than in BALB/c mice. However, their glomerular accumulation of macrophages and T cells was significantly greater. Complement depletion attenuated neutrophil influx and proteinuria in BALB/c mice but did not affect T cell or macrophage accumulation or proteinuria in C57BL/6 mice. CD4+ T cell depletion significantly reduced glomerular macrophage, T cell influx, and proteinuria in C57BL/6 mice, but had no effect on proteinuria or neutrophil influx in BALB/c mice. Thus, immune responses to planted glomerular antigens in Th2-prone mice induce acute injury as a result of antibody deposition, complement activation, and neutrophil influx, whereas immune responses to the same antigen in Th1-prone mice induce delayed-type hypersensitivity-like lesions in affected glomeruli.