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) 的倡议，印度儿童首次获得抗逆转录病毒治疗 (ART)。主要中心将遵循治疗 15 岁以下艾滋病毒感染儿童的规定，包括结核病研究所（PI，S Swaminathan 博士），该研究所是印度南部的一个主要儿科艾滋病毒中心。该项目由美国儿科免疫学家 (S. Pahwa) 和印度 PI 合作，旨在提供有关 HIV 疾病发病机制的见解，这对全球 HIV 感染者的未来管理具有重要意义。这些研究还将为后续具有挑战性和创新性的治疗方案、临床试验和未来的疫苗研究奠定基础。我们的具体目标围绕以下假设： 1. 开始 ART 之前 NaTve CD4 T 细胞的最低点预测 CD4 T 细胞重建的能力； 2. CD127+ CDS T 细胞的丢失或 CD127-CD8 T 细胞的扩增与异常的免疫激活和疾病进展相关。 3. 树突状细胞功能的重建对于功能性免疫重建至关重要。这些研究将通过流式细胞术和实时 PCR 进行新颖且最新的免疫学评估，在需要最少血量的检测中应用来表征 HIV 感染儿童的免疫状态，包括那些开始接受 ART 治疗的儿童和那些尚未达到资格标准的儿童用于抗逆转录病毒治疗。所有新的免疫检测都将前瞻性地进行，并在当前已建立的疾病进展指标（即 CD4 计数和病毒载量）的背景下分析结果。拟议的研究将提供对艾滋病毒疾病发病机制的深入了解，这对全球艾滋病毒感染者的未来管理具有影响。这些研究还将为后续具有挑战性和创新性的治疗方案以及未来的疫苗研究奠定基础。