THE IMMUNOMODULATORY EFFECTS OF DNA IN SLE

描述：（改编自研究者摘要）：系统性狼疮 红斑狼疮（SLE）是一种原型自身免疫性疾病，其特征在于 抗DNA抗体（anti-DNA）这些抗体作为 诊断和预后意义。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影响， 用细菌DNA免疫正常和自身免疫小鼠。这个DNA是 由于其含有刺激B细胞的CpG基序， 活化和细胞因子产生。在正常小鼠中，细菌DNA可以诱导 免疫DNA特异性抗体，而在自身免疫NZB/NZW小鼠中， 免疫导致产生具有SLE特性的自身抗体 反DNA相比之下，用哺乳动物DNA免疫是没有效果的， 这表明该DNA可能具有抑制活性。到 进一步分析该模式，提出了3个具体目标： 1)目的：探讨诱导抗DNA产生的遗传基础， 研究了用细菌DNA免疫的各种近交系和同类系菌株， 哺乳动物DNA以及合成寡核苷酸。 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和其他免疫刺激物引起。的 还将测试合成寡核苷酸的效果。 3)探讨细菌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， 将在体外系统中评估它们的反调节。所有这些 研究将阐明外源和自身DNA抗原可以 调节自身免疫过程。

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.