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，仍然是一种 世界范围内的健康问题，无论是在发展中国家还是在 美国和欧洲。MV导致约150万至200万人死亡 每年，主要是5岁以下的儿童。其中一个 麻疹病毒感染的特点是长期异常 细胞免疫(CMI)，导致免疫抑制和 被认为是导致继发性心脏病易感性增加的原因 感染是大多数发病率的主要原因， 疾病的死亡率。造成这一现象的根本机制(S) 免疫抑制作用尚不清楚。白介素12(IL-12)是一个重要的 细胞介导性反应的调节因子，主要由 单核/巨噬细胞。已有研究表明，在体外感染 带有MV的单核细胞特异性地下调IL-12的产生。类似 当CD46作为调节因子的补充时，对IL-12产生的影响 蛋白质和MV的细胞受体，要么通过抗体， 聚合C3b(CD46的内源性补体配体)，或与 瞬时表达MV血凝素。这些发现提供了一个可信的 MV诱导抑制CMI的机制。这项提议将检验 假设MV对CD46的利用导致抑制 CMI通过抑制IL-12的产生而发挥作用。目标是定义 CD_(46)抑制IL-12产生的机制(S) 人外周血单个核细胞对IL-12的反应 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.