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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 大多数HIV感染患者在疾病过程中的某个时候会出现肺部并发症。 高效抗逆转录病毒疗法（HAART）的出现大大降低了肺部感染的发病率。 虽然感染仍然占主导地位，一些患者在开始HAART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疾病（IRD），可影响高达25%的开始HAART的患者。 IRD可能是致命的，并且在某些患者中经常类似于活动性肺部感染。 因此，它可能是一个困难的诊断，并有助于发病率和过度的临床试验。 早期肺部IRD通常是由HAART开始时的潜伏或未识别的感染引起的。 这些感染因子为IRD中的免疫病理学应答提供了底物。 因此，对IRD风险人群进行分层并评估其长期结果变得越来越重要，特别是随着全球接受HAART治疗的患者数量的增加。 我们假设肺IRD在临床上被低估，并由不平衡的Th 1应答介导。我们建议通过进行连续CT扫描、临床评估和支气管镜检查来解决这一假设，以在开始HAART的患者中收获肺T细胞。 将对肺和血液T细胞亚群进行细胞因子测量、流式细胞术和TREC分析，以评估初始或记忆细胞是否负责Th 1介导的IRD。 这些研究还将提供有关发病率、结局和IRD治疗策略的免疫学基础的信息。

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.