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
Maeda, T.; Nomoto, K.
Journal of Rheumatology 22(12): 2259-2265
1995
ISSN/ISBN: 0315-162X PMID: 8835559 Document Number: 449526
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 times DBA/2)F-1 mice inoculated with 5 times 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 mu-g either on Day 2 or Day 21, followed 5 days later by another administration of 200 mu-g. 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. Conclusion: 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.