IMMUNOLOGY DEVELOPMENTAL RESEARCH

免疫学发展研究

• 批准号: 3746824
• 负责人: CAROLINE C WHITACRE
• 金额: --
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3746824
• 关键词: AIDS vaccines; CD4 molecule; CD8 molecule; HIV envelope protein gp120; HIV infections; T lymphocyte; cooperative study; disease /disorder prevention /control; flow cytometry; homosexuals; human immunodeficiency virus; human subject; human therapy evaluation; immunologic assay /test; interleukin 2; lymphocyte proliferation; polymerase chain reaction; prognosis; sex behavior; virion; virus antigen; virus protein

Infection with the human immunodeficiency virus (HIV-1), the causative agent for the acquired immunodeficiency syndrome (AIDS) leads to a progressive decline in the number of CD4+ lymphocytes, ultimately resulting in a profound immunosuppression. With the introduction of new anti- retroviral and immunostimulatory therapies, it has become clear that the surrogate markers used at present, CD4 lymphocyte number and serum p24 antigen, are not sensitive enough to permit a rapid evaluation of new treatment modalities, particularly in the early stages of HIV infection. We have applied the technique of limiting dilution analysis (LDA) to HIV- infected population. The LDA is a sensitive and quantitative means for measuring immune competence, allowing the estimation of the frequency of lymphocytes responsive to a given antigen. Using this approach, we have shown that lymphocyte populations reactive with recall antigens such as tetanus toxoid are present and functional in HIV-infected persons at all stags of disease. However, we have also employed the LDA for detection of immunologic responses directed against immunodominant HIV envelope peptides. Frequencies of reactive lymphocytes, although readily detectable, are low in asymptomatic HIV-infected individuals. In this application, we propose to refine the LDA approach for measuring anti-HIV immune responses by investigating the following specific research questions: Can the sensitivity of the HIV-specific LDA be further increased? and What are the characteristics of the responding cell population in the HIV-specific LDA? Thereafter, specific clinically relevant research questions can be pursued. First, do HIV-specific immune responses play a role in protection from HIV infection by examination of couples where one sex partner is seropositive and the other seronegative. Second, do HIV-specific immune responses predict the course of HIV disease by performing LDA ama;uses retrospectively on those persons who progress versus those who remain asymptomatic. Third, do HIV-specific immune responses correlate with clinical efficacy in vaccine trials by measuring the anti-HIV immune response in those persons enrolled in ACTG protocol 137 (immunization of asymptomatic HIV-infected persons with gp160). From our results thus far, it is clear that the LDA provides an extremely sensitive approach for assessing immune competence and should be of value in evaluating the relevance of the HIV-specific cellular immune response as a predictor of disease progression or response to therapy.

人类免疫缺陷病毒（HIV-1）感染，病因 获得的免疫缺陷综合征（AIDS）的药物导致 CD4+淋巴细胞数量的逐渐下降，最终导致 在深刻的免疫抑制中。 随着新的反 - 逆转录病毒和免疫刺激性疗法，很明显 目前使用的替代标记，CD4淋巴细胞数和血清P24 抗原，不够敏感，无法快速评估新的 治疗方式，特别是在HIV感染的早期。 我们已经将限制稀释分析（LDA）的技术应用于HIV- 感染人群。 LDA是一种敏感和定量的手段 测量免疫能力，允许估计 淋巴细胞对给定的抗原有反应。 使用这种方法，我们有 表明淋巴细胞种群用回忆抗原（例如 破伤风毒素存在并在艾滋病毒感染者中起作用 疾病的雄鹿。 但是，我们还采用了LDA检测 针对免疫主导HIV信封的免疫反应 肽。 反应性淋巴细胞的频率，尽管很容易 可检测到的无症状艾滋病毒感染者低。 在这个 应用，我们建议完善测量抗HIV的LDA方法 通过研究以下特定研究来免疫反应 问题：HIV特异性LDA的敏感性可以进一步 增加？而响应单元的特征是什么 HIV特异性LDA中的人口？ 此后，特定于临床 可以提出相关的研究问题。 首先，做艾滋病毒特异性免疫 通过检查 一个性伴侣是血清阳性的，另一种性伴侣。 其次，艾滋病毒特异性免疫反应预测了艾滋病毒疾病的病程 通过执行LDA AMA；追溯使用那些进步的人 与那些无症状的人相比。 第三，做HIV特异性免疫 通过测量疫苗试验中临床功效的反应与临床功效相关 ACTG协议中招收的人的抗HIV免疫反应137 （具有GP160的无症状HIV感染者的免疫接种）。 来自我们的 结果到目前为止，很明显，LDA提供了极其敏感的 评估免疫能力的方法，应具有价值 评估HIV特异性细胞免疫反应的相关性 预测疾病进展或对治疗的反应。