IMMUNOSUPPRESSION IN MEASLES--THE ROLE OF IL 12 AND CD46

描述：麻疹病毒（MV）是一种重要的病原体， 发展中国家和非洲国家的全球健康问题 美国和欧洲 MV造成约150万至200万人死亡 主要是5岁以下的儿童。 之一 麻疹病毒感染的特点是长期异常， 细胞介导的免疫（CMI）导致免疫抑制， 被认为有助于增加对继发性 感染，这是主要负责大部分的发病率， 疾病的死亡率。 造成这种情况的根本机制 免疫抑制是未知的。 白细胞介素12（IL-12）是一种重要的 细胞介导反应的调节因子，主要由 单核细胞/巨噬细胞。 已经表明，体外感染 具有MV的单核细胞特异性下调IL-12的产生。 类似 当CD 46，一种补体调节因子， 蛋白质和MV的细胞受体，通过抗体交联， 聚合的C3 b（CD 46的内源性补体配体），或与 瞬时表达的MV血凝素。 这些发现提供了一个合理的 MV诱导的CMI抑制机制。 该提案将测试 MV利用CD 46导致抑制CD 46表达的假设， CMI通过抑制IL-12的产生。 目标是定义 CD 46介导的抑制IL-12产生的机制，以及 表征来自以下患者的外周血单核细胞中的IL-12应答： 麻疹患者

DESCRIPTION: Measles virus (MV) is an important pathogen that remains a worldwide health problem both in developing countries as well as in the United States and Europe. MV causes approximately 1.5 to 2 million deaths per year, primarily in children under 5 years of age. One of the characteristics of measles virus infections is prolonged abnormalities of cell-mediated immunity (CMI) which results in immunosuppression and is thought to contribute to the increased susceptibility to secondary infections which is primarily responsible for most of the morbidity and mortality of the disease. The underlying mechanism(s) responsible for this immunosuppression is not known. Interleukin 12 (IL-12) is an important regulator of the cell-mediated response which is produced primarily by monocytes/macrophages. It has been shown that in vitro infection of monocytes with MV specifically downregulates production of IL-12. Similar effects on IL-12 production are seen when CD46, a complement regulatory protein and the cellular receptor for MV, is crosslinked either by antibody, polymerized C3b (an endogenous complement ligand for CD46), or with transiently expressed MV hemagglutinin. These finding provide a plausible mechanism for the MV-induced suppression of CMI. This proposal will test the hypothesis that the utilization of CD46 by MV results in suppression of CMI through the inhibition of IL-12 production. The goals are to define the mechanism(s) of CD46-mediated suppression of IL-12 production, and to characterize IL-12 responses in perpherial blood mononuclear cells from patients with measles.