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

Authors
Journal
American Journal Of Pathology
0002-9440
Publisher
Elsevier
Publication Date
Volume
179
Issue
6
Identifiers
DOI: 10.1016/j.ajpath.2011.08.017
Disciplines
  • Medicine

Abstract

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 T H1 and T H17 cells, using Fab 2 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 T H1 or T H17 cell lines were injected into mice that were also given peptide-conjugated Fab 2 or unconjugated Fab 2 control, giving four experimental groups. After 21 days crescentic glomerulonephritis was seen in mice receiving T H17 cells and peptide-conjugated Fab 2 but in none of the other three groups. These results suggest that T H17 but not T H1 cells can induce crescentic glomerulonephritis.

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