PULMONARY CD4+ T-CELL RE-POPULATION IN IMMUNE RECONSTITUTION SYNDROME

免疫重建综合征中肺 CD4 T 细胞的重新增殖

• 批准号: 7717564
• 负责人: KENNETH S KNOX
• 金额: $ 1.04万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7717564
• 关键词: Address; Affect; Blood; Bronchoscopy; Cells; Clinical assessments; Complication; Computer Retrieval of Information on Scientific Projects Database; Diagnosis; Disease; Flow Cytometry; Foundations; Funding; Grant; HIV Infections; Harvest; Highly Active Antiretroviral Therapy; Immune; Immune system; Immunologics; Incidence; Infection; Infectious Agent; Institution; Lung; Measurement; Mediating; Memory; Morbidity - disease rate; Numbers; Outcome; Patients; Population; Research; Research Personnel; Resources; Risk; Source; Syndrome; T-Cell Receptor-Rearrangement Excision DNA Circles; T-Lymphocyte; T-Lymphocyte Subsets; Time; United States National Institutes of Health; X-Ray Computed Tomography; cytokine; reconstitution; research clinical testing; response; restoration

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Most patients with HIV infection will have a pulmonary complication at some point during the course of their disease. The advent of highly active antiretroviral therapy (HAART) has dramatically decreased the incidence of pulmonary infections. Although infections still predominate, some patient have a paradoxical worsening after initiation of HAART despite evidence of a recovering immune system. This phenomenon is termed immune restoration disease (IRD) and can affect up to 25% of patients who initiate HAART. IRD can be fatal and frequently mimics active pulmonary infection in some patients. As such, it can be a difficult diagnosis and contribute to morbidity and excessive clinical testing. Early pulmonary IRD is usually caused by latent or unrecognized infections at the time HAART is initiated. These infectious agents provide the substrate for the immunopathological response in IRD. Stratifying people at risk for IRD and assessing their longterm outcome is thus increasingly important, especially as the number of patients treated with HAART increases worldwide. We hypothesize that pulmonary IRD is clinically underrecognized and mediated by unbalanced Th1 responses. We propose to address this hypothesis by performing sequential CT scans, clinical assessment and bronchoscopies to harvest lung T cells in patients starting HAART. Cytokine measurements, flow cytometry, and TREC analysis will be performed on lung and blood T cell subsets to assess if na¿ve or memory cells are responsible for Th1-mediated IRD. These studies also will provide information on incidence, outcome, and the immunologic foundation for IRD treatment strategies.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 大多数感染艾滋病毒的患者会在疾病过程中的某个时候出现肺部并发症。高效抗逆转录病毒疗法(HAART)的出现极大地降低了肺部感染的发生率。尽管感染仍然占主导地位，但一些患者在HAART开始后出现矛盾的恶化，尽管有证据表明免疫系统正在恢复。这种现象被称为免疫恢复性疾病(IRD)，可影响高达25%的启动HAART的患者。IRD可能是致命的，在一些患者中经常模仿活动性肺部感染。因此，它可能是一个很难诊断的疾病，并导致发病率和过多的临床检测。早期肺部IRD通常是在HAART开始时由潜伏或未被识别的感染引起的。这些感染性物质为IRD的免疫病理反应提供了底物。因此，对IRD高危人群进行分层并评估他们的长期结果变得越来越重要，尤其是在全世界接受HAART治疗的患者数量增加的情况下。我们假设肺IRD在临床上被低估，并由失衡的Th1反应介导。我们建议通过进行连续的CT扫描、临床评估和支气管镜检查来解决这一假设，以获取开始HAART的患者的肺T细胞。将对肺和血T细胞亚群进行细胞因子测量、流式细胞术和TREC分析，以评估是否NA或记忆细胞负责Th1介导的IRD。这些研究还将为IRD的治疗策略提供发病率、结果和免疫学基础的信息。