title: Anti-T cell receptor antibody treatment of mice with lupus-like graft versus host disease: suppression of glomerulonephritis without reduction in anti-DNA antibody levels.
abstract: OBJECTIVE
  To evaluate the therapeutic efficacy of anti-alpha beta T cell receptor (TCR) monoclonal antibody (Mab) on lupus-like graft versus host disease (GVHD). An attempt was also made to deduce the role of T cells in the progression of lupus nephritis.
  
  
  METHODS
  [C57BL/6 x DBA/2]F1 mice inoculated with 5 x 10(7) DBA/2 spleen cells developed a variety of immunostimulatory symptoms, including the hyperproduction of anti-dsDNA antibodies and severe glomerulonephritis. Anti-alpha beta TCR Mab was injected intraperitoneally at a dose of 400 micrograms either on Day 2 or Day 21, followed 5 days later by another administration of 200 micrograms.
  
  
  RESULTS
  Short term treatment with anti-alpha beta TCR Mab starting 2 days after cell transfer markedly reduced the serum anti-dsDNA antibody (IgG) titers and virtually abolished the induction of glomerulonephritis. Anti-alpha beta TCR treatment begun on Day 21 was also found effective in preventing the development of glomerulonephritis. In this case, however, the serum anti-dsDNA IgG titers were not significantly reduced compared with untreated GVHD controls. Immunohistochemical staining of the kidney with antimouse IgG + IgM detected no antibody deposition in the glomerulus either in the mice given delayed anti-alpha beta TCR treatment or in the mice treated prophylactically with anti-alpha beta TCR Mab, despite the high titers of serum anti-dsDNA IgG observed in the former group. In contrast, massive antibody deposition was regularly detectable in the glomerulus of the untreated GVHD controls.
  
  
  CONCLUSIONS
  Our report demonstrates the therapeutic potential of anti-alpha beta TCR Mab for lupus-like disease, while suggesting that some help from cellular immunity is likely required for the hyperproduced autoantibodies to become deposited in the glomerulus in this model.
authors.affiliation: Department of Immunology, Kyushu University, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Maeda
authors.forename: K
authors.initials: K
authors.lastname: Nomoto
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D004247:DNA / Q000276:immunology*; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology / Q000517:prevention & control*; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000097:blood / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008181:Lupus Nephritis / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011507:Proteinuria / Q000188:drug therapy / Q000517:prevention & control; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors*; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D011948:Receptors, Antigen, T-Cell; D004247:DNA