CD4+ T CELLS PROMOTE EARLY ATHEROSCLEROSIS

描述（改编自研究者摘要）：临床动脉粥样硬化 涉及慢性低度炎症，涉及免疫介质， 心血管疾病（CVD）。T淋巴细胞约占20% 动脉粥样硬化纤维帽中的细胞，尽管存在争议， 缺乏T细胞的患者比免疫正常的患者发生更小的主动脉病变 动物细胞因子是影响许多不同类型的细胞因子的多效性因子。 细胞，具有多种生物学效应。T细胞可以通过免疫细胞化学分类。 它们产生的细胞因子类型。Th 1细胞产生IFN、IL-2和TNF，而Th 2细胞产生IFN、IL-2和TNF 细胞产生IL-4、IL-6和IL-10。许多因素影响Th细胞的偏向性， 确定显性亚型反应。这些因素包括：细胞因子环境 在Th 0细胞活化过程中，抗原呈递细胞的类型，其主要 组织相容性复合体（MHC）II类抗原单倍型，表达 辅助分子如B7-1/B7-2、T细胞的浓度和类型 表位，以及存在额外的调节细胞，如天然的 杀伤细胞和表达T细胞受体的T淋巴细胞。在许多 疾病，易感性或抗性对应于任一种的优势 Th 1或Th 2细胞反应。申请人假设，在小鼠中， 动脉粥样硬化，Th 1细胞偏好赋予易感性，而Th 2细胞偏好赋予易感性。 偏见促进了抵抗。PI将通过调节Th来证实这一假设 使用三种不同的方法对Th 1或Th 2表型进行偏倚。 特异性目标1将通过外源性施用以下物质来调节免疫偏离： IL-12（Th 1-诱导）或IL-4（Th 2-诱导）细胞因子或通过使用细胞因子 敲除小鼠Specific Aim 2将使用放射嵌合小鼠， IA和IE II类MHC分子转基因的C57 BL/6株。类MHC II IA分子与Th 1偏倚和动脉粥样硬化相关 而IE分子与Th 2偏倚和CVD相关， 阻力具体目标3将研究CD 4 + T细胞在 动脉粥样硬化形成，并评估这些细胞是否促进Th 1细胞优势。

DESCRIPTION (Adapted from Investigator's Abstract): Clinical atherosclerosis involves chronic low-grade inflammation, implicating immune mediators in cardiovascular disease (CVD). T lymphocytes comprise approximately 20 percent of the cells in the atheroma fibrous cap, and, although controversial, mice deficient in T cells develop smaller aortic lesions than immunocompetent animals. Cytokines are pleiotrophic factors that affect many different types of cells and have various biological effects. T cells can be categorized by the types of cytokines they produce. Th1 cells make IFN, IL-2 and TNF, whereas Th2 cells make IL-4, IL-6, and IL-10. Many factors influence Th cell bias and determine dominant subtype response. These include: the cytokine environment during Th0 cell activation, the type of antigen-presenting cell, its major histocompatibility complex (MHC) class II antigen haplotype, expression of accessory molecules such as B7-1/B7-2, the concentration and type of T cell epitope, and the presence of additional regulatory cells, such as natural killer cells and T lymphocytes expressing the T cell receptor. In many diseases, susceptibility or resistance corresponds to the dominance of either Th1 or Th2 cell responses. The applicant hypothesizes that in murine atherosclerosis, a Th1 cell bias confers susceptibility, whereas, a Th2 cell bias promotes resistance. The PI will confirm this hypothesis by modulating Th bias towards either the Th1 or Th2 phenotype using three distinct methods. Specific Aim 1 will modulate immune deviation by exogenous administration of IL-12 (Th1-inducing) or IL-4 (Th2-inducing) cytokines or by using cytokine knockout mice. Specific Aim 2 will use irradiation chimeric mice made between C57BL/6 strains transgenic for IA and IE class II MHC molecules. The MHC class II IA molecule is associated with a Th1 bias and atherosclerosis susceptibility, whereas, the IE molecule is associated with Th2 bias and CVD resistance. Specific Aim 3 will investigate the role of CD4+ T cells in atherogenesis and evaluate whether these cells promote Th1 cell dominance.