DC-INDUCED HIV-SPECIFIC T CELL IMMUNITY

DC 诱导的 HIV 特异性 T 细胞免疫

• 批准号: 6077841
• 负责人: Tyler J. Curiel
• 金额: $ 25.8万
• 依托单位: BAYLOR RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6077841
• 关键词: AIDS education /prevention; Adenoviridae; CD14 molecule; CD34 molecule; CD40 molecule; HIV infections; T lymphocyte; cellular immunity; cellular pathology; chemokine; clinical research; colony stimulating factor; cytokine; cytotoxicity; dendritic cells; helper T lymphocyte; human subject; macrophage; tissue /cell culture; transfection /expression vector; virus DNA; virus antigen; virus replication

DESCRIPTION: (Adapted from Applicant's Abstract) Immunity to HIV infection includes both cellular and humoral mechanisms. Dendritic cells (DCs) are good candidates to elicit HIV-specific immunity but optimal means to use them are not established. Three significant variables are i) the specific DC subset involved, 2) the antigens (Ags) used, and iii) the route of Ag acquisition by DCs. There are 3 well-characterized DC subsets identified in humans: Langerhans, interstitial, and lymphoid DCs. Several studies show that DCs elicit HIV-specific cellular immunity, but only studied monocyte-derived DCs. Ag formulation (apoptotic vs. necrotic) and acquisition pathway also influence elicited immunity, although little systematic study has been reported. A novel DC type, the macrophage (M)-derived DC, may have advantages over other DC subsets in eliciting HIV-specific immunity. The goal is to determine which DC subsets, acquiring Ag in specific contexts, elicit immune effector cells thought to be important in preventing HIV infection, and in controlling HIV replication. The focus on induction of cellular immunity because of the investigators expertise in that area. The hypothesize is that if optimal DC subsets and Ag acquisition pathways are identified in vitro, then ultimately specific targeting strategies may be used to make a convenient vaccine preparation that does not require the ex vivo growth or manipulation of autologous DCs. There are 3 specific aims: #1: to determine the differential ability of 3 DC subsets, interstitial or epidermal DCs derived from CD34+ HPCs and DCs produced from M-CSF derived Macrophages to activate HIV gag, pol, env or nef-specific T cells when Ags are acquired in two distinct contexts (endogenous production or exogenous capture). #2: to determine whether the specific effector cells elicited are those thought to prevent HIV infection, examining cytotoxicity, and cytokine/chemokine production (THl/TH2 and TCl/TC2 immunity); and #3: to determine the non-cytolytic capacity of these elicited immune cells to inhibit HIV

描述：（改编自申请人的摘要）免疫对HIV感染 包括细胞和体液机制。树突状细胞（DC）很好 候选人获得艾滋病毒特异性免疫力，但使用它们的最佳方法是 未建立。三个重要变量是i）特定的DC子集 涉及2）使用的抗原（AGS），以及iii） DCS。人类中有3种良好的DC子集： Langerhans，间质和淋巴样DC。几项研究表明DCS 引起HIV特异性细胞免疫，但仅研究了单核细胞衍生的DC。 Ag公式（凋亡与坏死）和采集途径也会影响 尽管很少有系统的研究，但引起免疫力。小说 DC类型，巨噬细胞（M）衍生的DC，可能比其他DC具有优势 引发HIV特异性免疫的子集。目标是确定哪个DC 子集，在特定情况下获取AG，引起免疫效应细胞 被认为对防止艾滋病毒感染和控制艾滋病毒很重要 复制。着重于诱导细胞免疫，因为 研究人员在该领域的专业知识。假设是如果最佳DC 在体外鉴定了子集和AG采集途径，然后最终 特定的靶向策略可用于制造方便的疫苗 不需要体内生长或操纵的准备 自体DC。有3个具体目标：＃1：确定差分 衍生自CD34+ HPC的3个DC子集，间隙或表皮DC的能力 和由M-CSF衍生的巨噬细胞产生的DC，以激活HIV GAG，POL，ENV 当在两个不同的情况下获取AG时，或NEF特异性T细胞 （内源性产生或外源捕获）。 ＃2：确定是否 引起的特定效应细胞是被认为可以防止HIV感染的细胞， 检查细胞毒性和细胞因子/趋化因子的产生（THL/TH2和TCL/TC2 免疫）;和＃3：确定这些引起的非溶解能力 免疫细胞抑制HIV