自身免疫性疾病是由自身反应性T及B细胞异常活化所致。涉及疾病30余种。发病机制尚未明确。若能特异性阻断或削弱T、B细胞异常应答即可发挥治疗作用。本课题旨在运用自行研制的基因工程抗人B7-1双价抗体可同时识别人与小鼠B7-1分子的特性。从事以下研究：1.采用化学法（pristane）建立类拟人类系统性红斑狼疮(SLE)发病过程及临床表现的小鼠（C57BL/J6 (B6)）狼疮样肾病模型为研究切入点；2.运用B7-1双价抗体序贯治疗，以阻抑APC-T-B信号轴；3.通过血清学（血尿素氮、自身抗体、抗核抗体）及肾脏病理损伤评价（蛋白尿、肾小球肾炎评分、免疫复合物等）指标的动态监测，考察抗体的治疗效应；4.通过系统分析疾病模型及抗体干预前、后免疫学指标（细胞因子、细胞凋亡、免疫细胞活化及功能）及信号转导通路中重要转录因子NF-κB的动态变化，探究自身抗原产生及活化的分子机制。

Autoimmune diseases is characterized by a global loss of self-tolerance with activation of hyper-reactive T and B cells leading to production of pathogenic autoantibodies and tissue injury, Among more than 30 kinds of autoimmune disease, systemic lupus erythematosus (SLE) is representative. Despite substantial research on SLE, the etiology and pathogenesis are still not well understood. Due to these obstacles, the disease treatment has lagged behind many other diseases, seldom therapies were specific and high effectual. Only one new drug for lupus was approved by the United States Food and Drug Administration (FDA) in the last 50 years. As a promising kind of therapy on SLE, infusion with monoclonal antibodies or other specific proteins that specifically inhibit or interfere with T cell and/or B cell hyper-reaction is revolutionizing the treatment of autoimmune disorders. The steps of our investigation were: 1. To develop the animal model of SLE. Intraperitoneal injection of the hydrocarbon oil pristane into C57BL/J6 (B6) mice leads to lupus-like autoimmune syndrome, This model is well suited to investigate the pathogenesis process and clinic manifestation of SLE as human-beings. 2. To treat the lupus-like model by anti-B7-1 diabody (only containing two VH and VL fragments), which was generated by our lab, in order to suppress the APC-T -B cell signal pathway.? ??3. To investigate the therapeutic effect of B7-1 diabody, the serology of BUN, autoantibody, antinuclear antibody, evaluation of renal disease(proteinuria, glomerulonephritis score, immune-complexes deposition) were dynamic monitored. 4. To study the molecular mechanism of the autoantibody generation and activation by analyzing the immunology indexes of lupus-like disease model systematically, including cytokines, cell apoptosis, immune cell activation, immune cell function, and the dynamic changing process of NF-κB acting as a very important transcription factor for the transduction signal pathways.