Pulmonary CD4+ T-Cell Repopulation in Immune Reconstituion Syndrome

免疫重建综合征中的肺 CD4 T 细胞增殖

基本信息

批准号：
7448545
负责人：
KENNETH S KNOX
金额：
$ 30.24万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-29 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7448545
关键词：
Acquired Immunodeficiency Syndrome Address Adverse drug effect Affect Alveolar Alveolitis Antigens Autoimmune Process Blood Blood Vessels Bronchoscopy CD4 Lymphocyte Count CD4 Positive T Lymphocytes CD4/CD8 ratio procedure Caring Cell Count Cell Death Cell physiology Cells Clinical Clinical Trials Clinical assessments Complication Cytomegalovirus Data Diagnosis Diagnostic Disease Disease Progression Enrollment Environment Equilibrium Flow Cytometry Foundations Frequencies Genetic Polymorphism Genotype HIV Harvest Health Highly Active Antiretroviral Therapy Human Image Immune Immune System Diseases Immune response Immune system Immunologics Immunosuppression Incidence Infection Infectious Agent Inflammatory Inflammatory Response Longitudinal Studies Lung Lymphocyte MHC Class II Genes Measurement Mediating Memory Modeling Morbidity - disease rate Mycobacterium tuberculosis Numbers Opportunistic Infections Outcome Patients Pharmaceutical Preparations Phase Phenotype Population Process Prophylactic treatment Prospective Studies Protocols documentation Public Health Rate Reaction Research Personnel Resolution Risk Risk Factors Role Sarcoidosis Site Subgroup Syndrome T-Cell Receptor-Rearrangement Excision DNA Circles T-Lymphocyte T-Lymphocyte Subsets Th1 Cells Therapeutic immunosuppression Time Tissues Uveitis Viral Load result Virus Diseases Work X-Ray Computed Tomography antiretroviral therapy base clinical phenotype cohort cytokine follow-up novel pathogen programs prospective reconstitution research clinical testing response restoration trend

项目摘要

DESCRIPTION (provided by applicant): Most patients with Human Immunodeficiency Virus (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 patients 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. 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. However, late pulmonary IRD frequently manifests as sarcoidosis and is caused by unknown antigens. Stratifying people at risk for IRD and assessing their long term 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 therapy. Cytokine measurements, flow cytometry, and TREC analysis will be performed on lung and blood T cell subsets to assess if naive or memory cells are responsible for Th1-mediated IRD. Specific aims include: 1. To define a large, well-characterized clinical cohort of HIV-infected subjects for longitudinal study of IRD. 2. To determine the mechanisms of CD4 repopulation of the lung and 3. To define predictors of early and late pulmonary IRD based on clinical and immunological parameters. This work will have significant implications on clinical issues in HIV infected subjects, including predicting who is at risk for IRD and the 3 year outcome of patients with IRD. These studies also will provide the immunologic foundation for treatment strategies. Public Health Statement: As more patients worldwide are treated with anti-HIV drugs, the "side effects" of these drugs require study. Patients who are at risk for these therapy-related problems need to know if their long term health is affected.

描述（由申请人提供）：大多数患有人类免疫缺陷病毒（HIV）感染的患者在疾病过程中的某个时刻将患有肺部并发症。高度活跃的抗逆转录病毒疗法（HAART）的出现大大降低了肺部感染的发生率。尽管感染仍然占主导地位，但尽管有证据表明免疫系统恢复了，但有些患者在HAART启动后仍有矛盾的恶化。该现象称为免疫恢复疾病（IRD），可能会影响启动HAART的患者中多达25％。 IRD可能是致命的，并且经常模仿活跃的肺部感染。因此，这可能是一个困难的诊断，并有助于发病率和过度的临床测试。早期的肺IRD通常是由HAART启动的潜在或未识别的感染引起的。这些感染剂为IRD中的免疫病理反应提供了底物。然而，晚期肺IRD经常表现为结节病，是由未知抗原引起的。因此，将有IRD风险的人分层并评估其长期结局的越来越重要，尤其是随着在全球范围内接受HAART治疗的患者人数增加。我们假设肺部IRD在临床上被识别和介导的TH1反应不平衡。我们建议通过进行顺序的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治疗的患者中收获肺T细胞。细胞因子测量，流式细胞仪和TREC分析将在肺和血液T细胞亚群上进行，以评估天真或记忆细胞是否负责Th1介导的IRD。具体目的包括： 1。定义一个大型的，良好的临床临床群体，用于IRD的纵向研究。 2。确定肺CD4重生的机制和3。根据临床和免疫学参数定义早期和晚期IRD的预测因子。这项工作将对受艾滋病毒感染受试者的临床问题产生重大影响，包括预测谁面临IRD的风险和IRD患者的3年结果。这些研究还将为治疗策略提供免疫学基础。公共卫生声明：随着全世界越来越多的患者接受抗HIV药物的治疗，这些药物的“副作用”需要研究。面临这些与治疗有关的问题的患者需要知道长期健康是否受到影响。