Regulatory interactions of αβ and γδ T cells in glomerulonephritis

A. R. Rosenkranz, S. Knight, S. Sethi, S. I. Alexander, R. S. Cotran, T. N. Mayadas

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Background. Several lines of evidence suggest that cellular immune mechanisms contribute to glomerulonephritis. Methods. The roles of αβ and γδ 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)β and TCRδ 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 αβ or γδ T cells developed minimal proteinuria and glomerular lesions and had a significant reduction in macrophage accumulation compared with wild-type mice. In γδ T-cell-deficient mice, circulating levels and glomerular deposition of autologous IgG were comparable to wild-type levels, while αβ 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 (μ-chain-/-) developed similar proteinuria to that observed in wild-type mice. Conclusions. These studies suggest a proinflammatory role for both αβ and γδ 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 αβ and γδ T cells play a role in glomerular injury.

Original languageEnglish (US)
Pages (from-to)1055-1066
Number of pages12
JournalKidney international
Volume58
Issue number3
DOIs
StatePublished - 2000

Keywords

  • Cellular immunity
  • Inflammation
  • Macrophages
  • T cell receptor
  • Transgenic mice

ASJC Scopus subject areas

  • Nephrology

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