title: Regulatory interactions of alphabeta and gammadelta T cells in glomerulonephritis.
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.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Rosenkranz
authors.forename: S
authors.initials: S
authors.lastname: Knight
authors.forename: S
authors.initials: S
authors.lastname: Sethi
authors.forename: S I
authors.initials: SI
authors.lastname: Alexander
authors.forename: R S
authors.initials: RS
authors.lastname: Cotran
authors.forename: T N
authors.initials: TN
authors.lastname: Mayadas
mesh_terms: D000818:Animals; D000906:Antibodies; D001402:B-Lymphocytes / Q000276:immunology; D001485:Basement Membrane / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003165:Complement System Proteins / Q000032:analysis; D015870:Gene Expression / Q000276:immunology; D005921:Glomerulonephritis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D007111:Immunity, Cellular / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011507:Proteinuria / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000378:metabolism*
chemical_list: D000906:Antibodies; D007074:Immunoglobulin G; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D003165:Complement System Proteins