A Th1 Response Is Essential for Induction of Crescentic Glomerulonephritis in Mice

Abstract

Crescentic glomerulonephritis can be induced in rodents by injection of heterologous antibodies against the glomerular basement membrane. There is evidence that glomerular inflammation in that model represents a delayed–type hypersensitivity response to the heterologous immunoglobulin, whereas the antibody response is not important. The aim of the present study was to test this hypothesis. Delayed–type hypersensitivity is mediated by T cells with the Th1 phenotype. We compared mice immunized with rabbit immunoglobulin G in complete Freund’s adjuvant or in incomplete Freund’s adjuvant, producing, respectively, Th1– or Th2–biased responses to the antigen. Intravenous injection of rabbit antimouse glomerular basement membrane serum provoked proteinuria, infiltration with T cells and macrophages, as well as profound histological damage in the group treated with complete Freund’s adjuvant. There was no evidence of glomerulonephritis in the group which received incomplete Freund’s adjuvant. Deposits of mouse IgG along the glomerular basement membrane were similar in both groups. Thus, a Th1 response appears to be essential for the induction of glomerulonephritis in this model.