Regulatory Interactions of Alphabeta and Gammadelta T Cells in Glomerulonephritis

Kidney Int. 2000 Sep;58(3):1055-66. doi: 10.1046/j.1523-1755.2000.00263.x.

Abstract

Background: Several lines of evidence suggest that cellular immune mechanisms contribute to glomerulonephritis.

Methods: The roles of alphabeta and gammadelta 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)beta and TCRdelta 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 alphabeta or gammadelta T cells developed minimal proteinuria and glomerular lesions and had a significant reduction in macrophage accumulation compared with wild-type mice. In gammadelta T-cell-deficient mice, circulating levels and glomerular deposition of autologous IgG were comparable to wild-type levels, while alphabeta 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 (micro-chain-/-) developed similar proteinuria to that observed in wild-type mice.

Conclusions: These studies suggest a proinflammatory role for both alphabeta and gammadelta 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 alphabeta and gammadelta T cells play a role in glomerular injury.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies
  • B-Lymphocytes / immunology
  • Basement Membrane / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Complement System Proteins / analysis
  • Gene Expression / immunology
  • Glomerulonephritis / immunology*
  • Glomerulonephritis / metabolism*
  • Glomerulonephritis / pathology
  • Immunity, Cellular / immunology
  • Immunoglobulin G / immunology
  • Immunoglobulin G / metabolism
  • Kidney Glomerulus / immunology
  • Kidney Glomerulus / pathology
  • Macrophages / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Proteinuria / immunology
  • Proteinuria / metabolism
  • Proteinuria / pathology
  • RNA, Messenger / analysis
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism*
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*

Substances

  • Antibodies
  • Immunoglobulin G
  • RNA, Messenger
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • Complement System Proteins