THE IMMUNOMODULATORY EFFECTS OF DNA IN SLE

描述：(改编自调查人员摘要)：系统性红斑狼疮 红斑狼疮(SLE)是一种典型的自身免疫性疾病 产生DNA抗体(抗DNA)。这些抗体充当标志物。 对诊断和预后有重要意义。作为一个模型来阐明 这种反应的机制，我的实验室已经研究了 细菌DNA免疫正常小鼠和自身免疫小鼠。这种DNA是一种 强大的免疫原，因为它含有刺激B细胞的CpG基序 激活和细胞因子的产生。在正常小鼠中，细菌DNA可以诱导 在自身免疫的NZB/NZW小鼠中，针对免疫DNA的抗体， 免疫导致产生具有系统性红斑狼疮特性的自身抗体 抗DNA抗体。相比之下，用哺乳动物DNA免疫是没有效果的， 这表明这种DNA可能具有抑制活性。至 进一步分析该模型，提出了3个具体目标： 1)研究诱导抗DNA产生的遗传基础。 细菌DNA免疫多种自交系和同源菌株的研究 哺乳动物DNA以及人工合成的寡核苷酸。 2)研究哺乳动物DNA抑制免疫反应的能力 在体外系统中由细菌DNA和其他免疫刺激剂诱导。这个 合成寡核苷酸的效果也将得到测试。 3)评估细菌DNA诱导的一氧化氮和前列腺素的作用 产生抗体和细胞因子反应。这些调解人的作用和 它们的反调节作用将在体外系统中进行评估。加在一起，这些 研究将阐明外源和自身dna抗原可以 调节自身免疫的进程。

DESCRIPTION: (Adapted from the Investigator's abstract): Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the production of antibodies to DNA (anti-DNA). These antibodies serve as markers of diagnostic and prognostic significance. As a model to elucidate the mechanism of this response, my laboratory has studied the effects of immunization of normal and autoimmune mice with bacterial DNA. This DNA is a potent immunogen because of its content of CpG motifs that stimulate B cell activation and cytokine production. In normal mice, bacterial DNA can induce antibodies specific for the immunizing DNA while in autoimmune NZB/NZW mice, immunization leads to the production of autoantibodies with properties of SLE anti-DNA. In contrast, immunization with mammalian DNA is without effect, suggesting the possibility that this DNA may have inhibitory activities. To analyze further this model, 3 specific aims are proposed: 1) To investigate the genetic basis of induced anti-DNA production through study of a variety of inbred and congenic strains immunized with bacterial DNA, mammalian DNA as well as synthetic oligonucleotides. 2) To investigate the ability of mammalian DNA to inhibit immune responses elicited by bacterial DNA and other immune stimulants in in vitro systems. The effect of synthetic oligonucleotides will also be tested. 3) To assess the role of bacterial DNA-induced nitric oxide and prostaglandin production in antibody and cytokine responses. The role of these mediators and their counter-regulation will be assessed in in vitro systems. Together, these studies will clarify important steps by which foreign and self DNA antigen can modulate the course of autoimmunity.