Transferred Antigen-Specific TH17 but not TH1 Cells Induce Crescentic Glomerulonephritis in Mice

To explore the role of antigen-specific CD4+ T cells in glomerulonephritis, we administered ovalbumin 323-339 peptide conjugated to glomerular-binding polyclonal antibody and induced disease in RAG1−/− mice with CD4+ T cells from OT2 × RAG1−/− mice. These OT2 × RAG1−/− mice have a transgenic T-cell receptor specific for this peptide. When CD4+ T cells were primed in vivo, crescentic glomerulonephritis developed after 21 days in mice given peptide-conjugated glomerular-binding antibody but not unconjugated antibody control. We then investigated the relative roles of TH1 and TH17 cells, using Fab2 fragments of glomerular-binding antibody to exclude a role for antibody in this model. T cells from OT2 × RAG1−/− mice were polarized in vitro, and TH1 or TH17 cell lines were injected into mice that were also given peptide-conjugated Fab2 or unconjugated Fab2 control, giving four experimental groups. After 21 days crescentic glomerulonephritis was seen in mice receiving TH17 cells and peptide-conjugated Fab2 but in none of the other three groups. These results suggest that TH17 but not TH1 cells can induce crescentic glomerulonephritis.