Maeda T, Nomoto K
Department of Immunology, Kyushu University, Fukuoka, Japan.
J Rheumatol. 1995 Dec;22(12):2259-65.
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.
[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.
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.
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.
评估抗αβT细胞受体（TCR）单克隆抗体（Mab）对狼疮样移植物抗宿主病（GVHD）的治疗效果。同时试图推断T细胞在狼疮性肾炎进展中的作用。
接种5×10⁷个DBA/2脾细胞的[C57BL/6×DBA/2]F1小鼠出现了多种免疫刺激症状，包括抗双链DNA抗体过度产生和严重的肾小球肾炎。在第2天或第21天腹腔注射剂量为400微克的抗αβTCR Mab，5天后再注射200微克。
细胞移植后2天开始用抗αβTCR Mab进行短期治疗，显著降低了血清抗双链DNA抗体（IgG）滴度，几乎消除了肾小球肾炎的诱导。在第21天开始的抗αβTCR治疗也被发现对预防肾小球肾炎的发展有效。然而，在这种情况下，与未治疗的GVHD对照组相比，血清抗双链DNA IgG滴度没有显著降低。用抗小鼠IgG + IgM对肾脏进行免疫组织化学染色，在延迟给予抗αβTCR治疗的小鼠或用抗αβTCR Mab预防性治疗的小鼠的肾小球中均未检测到抗体沉积，尽管在前一组中观察到血清抗双链DNA IgG滴度很高。相比之下，在未治疗的GVHD对照组的肾小球中经常可检测到大量抗体沉积。
我们的报告证明了抗αβTCR Mab对狼疮样疾病的治疗潜力，同时表明在该模型中，自身抗体过度产生并沉积于肾小球可能需要细胞免疫的某些帮助。
