Innate and adaptive immunity in children starting anir*

开始无性繁殖的儿童的先天性和适应性免疫*

• 批准号: 7046310
• 负责人: Savita Pahwa
• 金额: $ 7.63万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7046310
• 关键词: AIDS therapy; India; antiAIDS agent; biomarker; cellular pathology; clinical research; cytokine receptors; dendritic cells; flow cytometry; helper T lymphocyte; human subject; human therapy evaluation; immunity; interferon gamma; interleukin 7; leukocyte count; patient oriented research; pediatric AIDS; polymerase chain reaction; receptor expression; tissue resource /registry

DESCRIPTION (provided by applicant): Access to antiretroviral therapy (ART) is becoming available to children in India for the first time through an initiative from the National AIDS Control Organization (NACO). The mandate for treating HIV infected children <15 years of age will be followed in major centers, including the Tuberculosis Research Institute (PI, Dr S Swaminathan) which is a major pediatric HIV center in South India. This project, between a US pediatric immunologist (S. Pahwa) and the Indian PI proposes to provide insights into HIV disease pathogenesis that have implications for future management of HIV infected subjects world wide. These studies will also lay the groundwork for subsequent challenging and innovative treatment protocols, clinical trials and future vaccine studies. Our specific aims are centered around the following hypotheses: 1. The nadir of NaTve CD4 T cells prior to starting ART predicts capacity for CD4 T Cell reconstitution; 2. Loss of CD127+ CDS T Cells or expansion of CD127-CD8 T Cells is associated with aberrant immune activation and disease progression, 3. Reconstitution of Dendritic Cell function is essential for functional immune reconstitution. These studies will apply novel and most current immunologic evaluations by flow cytometry and real time PCR in assays that require minimal blood volumes to characterize immunological status of HIV infected children, including those who initiate treatment with ART and those who have not progressed to reach eligibility standards for antiretroviral treatment. All new immunologic assays will be performed prospectively and the results analyzed in the context of current established indicators of disease progression, i.e. CD4 counts and virus load. The proposed investigations will provide insights into HIV disease pathogenesis that have implications for future management of HIV infected subjects world wide. These studies will also lay the groundwork for subsequent challenging and innovative treatment protocols, and future vaccine studies.

描述（由申请人提供）：通过国家艾滋病控制组织（NACO）的一项倡议，印度儿童获得了抗逆转录病毒疗法（ART）的访问。在主要中心，包括结核病研究所（PI，S Swaminathan博士），这是印度南部主要儿科HIV中心的主要中心（包括结核病研究所（PI，S Swaminathan博士），将遵循治疗艾滋病毒感染的儿童的任务。该项目，美国儿科免疫学家（S. Pahwa）和印度PI之间提出了对HIV疾病发病机理的见解，这些发病机理对全球艾滋病毒感染受试者的未来管理具有影响。这些研究还将为随后的具有挑战性和创新的治疗方案，临床试验和未来的疫苗研究奠定基础。我们的具体目的集中在以下假设围绕：1。启动ART之前的NATVE CD4 T细胞的Nadir预测CD4 T细胞重建的能力； 2。CD127+ CD T细胞的丧失或CD127-CD8 T细胞的扩展与异常的免疫激活和疾病进展有关，3。树突状细胞功能的重建对于功能免疫重建至关重要。这些研究将通过流式细胞仪和实时PCR应用新颖和大多数当前的免疫学评估，这些测定需要最少的血液量来表征受HIV感染的儿童的免疫学状态，包括那些对ART进行治疗的人以及未进步以达到抗逆转录病毒治疗的资格标准的人。所有新的免疫学分析将前瞻性地进行，并在当前疾病进展的指标，即CD4计数和病毒负荷的情况下进行分析。拟议的研究将提供对HIV疾病发病机理的见解，这对全球艾滋病毒感染受试者的未来管理具有影响。这些研究还将为随后的具有挑战性和创新的治疗方案以及未来的疫苗研究奠定基础。