Kim C, Siminovitch K A, Ochi A
Division of Neurobiology and Molecular Immunology, Samuel S. Lunenfeld Research Instiute, Mount Sinai Hospital, Toronto, Ontario, Canada.
J Exp Med. 1991 Dec 1;174(6):1431-7. doi: 10.1084/jem.174.6.1431.
The effects of biweekly intravenous injections of Staphylococcus Enterotoxin B (SEB) into autoimmune MRL-lpr/lpr (MRL/lpr) mice were investigated. Rather than causing the expansion of V beta 8+ T cells, SEB administration resulted in the reduction V beta 8+, CD4-CD8- "double-negative" (DN) T cells. This was shown by FACS analysis as this putative pathogenic population was diminished in both spleen and lymph node. The symptoms of systemic lupus erythematosus (SLE) in MRL/lpr, which include high titers of anti-DNA antibodies and circulating immune complexes and proteinuria, were reduced in SEB-treated mice in a dose-dependent manner. The clinical parameters of SLE in MRL/lpr, which include lymph node hyperplasia and necrotic vasculitis, were suppressed in 50-micrograms SEB-treated mice. T cells bearing V beta 6 T cell receptor, which does not interact with SEB, were not reduced with SEB administration. Thus, disease suppression was associated with a specific reduction in the number of V beta 8+, DN T cells. These results implicate a possible therapeutic role of superantigen-based immunotherapy in V beta-restricted, T cell-dominated clinical syndromes.
研究了每两周向自身免疫性MRL-lpr/lpr(MRL/lpr)小鼠静脉注射金黄色葡萄球菌肠毒素B(SEB)的效果。SEB给药并未导致Vβ8 + T细胞扩增,反而导致Vβ8 +、CD4 - CD8 - “双阴性”(DN)T细胞减少。流式细胞术分析表明,在脾脏和淋巴结中,这个假定的致病群体数量均减少。在接受SEB治疗的小鼠中,MRL/lpr小鼠系统性红斑狼疮(SLE)的症状,包括高滴度的抗DNA抗体、循环免疫复合物和蛋白尿,均呈剂量依赖性降低。在接受50微克SEB治疗的小鼠中,MRL/lpr小鼠SLE的临床参数,包括淋巴结增生和坏死性血管炎,均受到抑制。携带不与SEB相互作用的Vβ6 T细胞受体的T细胞,在给予SEB后数量未减少。因此,疾病抑制与Vβ8 +、DN T细胞数量的特异性减少有关。这些结果表明基于超抗原的免疫疗法在Vβ受限、T细胞主导的临床综合征中可能具有治疗作用。