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.

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.

• Authors: T Maeda, K Nomoto
• Journal: The Journal of rheumatology (J Rheumatol) Vol. 22 Issue 12 Pg. 2259-65 (Dec 1995) ISSN: 0315-162X [Print] Canada
• PMID: 8835559 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Antinuclear
• Antibodies, Monoclonal
• Immunoglobulin G
• Receptors, Antigen, T-Cell
• DNA

Topics

• Animals
• Antibodies, Antinuclear (blood)
• Antibodies, Monoclonal (pharmacology, therapeutic use)
• DNA (immunology)
• Female
• Glomerulonephritis (immunology, prevention & control)
• Graft vs Host Disease (immunology, prevention & control)
• Immunoenzyme Techniques
• Immunoglobulin G (blood, drug effects)
• Kidney (drug effects, immunology, pathology)
• Lupus Nephritis (immunology, prevention & control)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred DBA
• Proteinuria (drug therapy, prevention & control)
• Receptors, Antigen, T-Cell (antagonists & inhibitors)
• Spleen (cytology, immunology)