MHC CLASS I ANTIHIV SPECIFIC CD8 T LYMPHOCYTE RESPONSE IN CNS OF HIV PATIENTS

HIV 患者 CNS 中 MHC I 类抗 HIV 特异性 CD8 T 淋巴细胞反应

• 批准号: 6357119
• 负责人: Allison Anne Imrie
• 金额: $ 39.02万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6357119
• 关键词: AIDS dementia complex; HIV infections; MHC class I antigen; cooperative study; cytotoxic T lymphocyte; epitope mapping; genetic strain; human tissue; neuroimmunomodulation; pathologic process; virus infection mechanism; virus load

Recent findings from the applicant's laboratories have demonstrated that decreases in CSF HIV-1 RNA concentration are strongly associated with improvement in neuropsychological test performance. These results provide further evidence for the role of HIV-1 viral load in the pathogenesis of AIDS dementia complex (ADC). The general goal of the collaborative research proposed is to define the role of MHC class I- restricted, anti-HIV-1 specific CD8+ cytotoxic T lymphocyte (CTL) responses in the control of HIV-1 replication within the CNS. Studies are proposed to test the working hypothesis that HIV-associated cognitive impairment is due to loss of control of HIV-1 replication within the CNS, that this loss of control is a consequence of viral escape from CTL responses, and that viral escape from immune control results in selection for unique strains of HIV-1 within the CNS of patients with ADC. The project will be conducted as an integrated and coordinated collaboration between investigators at the University of Hawaii and the University of Washington. The applicant component of the project will focus on characterizing HIV-1-specific CTL responses in the CNS of HIV-1 infected subjects, and determining whether changes in epitotic sequences of CNS-derived HIV-1 strains affect recognition of such epitopes, cognitive dysfunction, and CSF HIV-1 viral load. The hypotheses to be tested in both components are closely interrelated as are the experimental designs, and will allow for the complementary expertise of the investigations to be applied in a maximally productive and mutually beneficial way. The collaboration will also provide ample opportunities for students and fellows at the University of Hawaii to obtain training in the basic neuroscience techniques to be implemented in the conduct of this research efforts. The results of the proposed research will be relevant to understand the role of MHC class 1-restricted, anti-HIV-specific CD8+ CTL in controlling HIV-1 RNA viral load within the CNS, and will contribute to understanding the relationship between CSF HIV-1 viral load and the pathogenesis of AIDS dementia complex.

申请人实验室的最新研究结果表明，CSF HIV-1 RNA 浓度的降低与神经心理学测试表现的改善密切相关。这些结果为 HIV-1 病毒载量在艾滋病痴呆症 (ADC) 发病机制中的作用提供了进一步的证据。拟议合作研究的总体目标是确定 MHC I 类限制性抗 HIV-1 特异性 CD8+ 细胞毒性 T 淋巴细胞 (CTL) 反应在控制 CNS 内 HIV-1 复制中的作用。提出的研究旨在检验以下工作假设：HIV 相关认知障碍是由于中枢神经系统内 HIV-1 复制失控所致，这种失控是病毒逃避 CTL 反应的结果，以及病毒逃避免疫系统的影响。控制结果导致 ADC 患者中枢神经系统内独特的 HIV-1 毒株的选择。该项目将作为夏威夷大学和华盛顿大学研究人员之间综合协调的合作进行。 该项目的申请人部分将重点关注 HIV-1 感染者 CNS 中 HIV-1 特异性 CTL 反应的特征，并确定 CNS 衍生的 HIV-1 毒株表位序列的变化是否影响对此类表位的识别、认知功能障碍和 CSF HIV-1 病毒载量。两个部分中要测试的假设与实验设计一样密切相关，并且将允许以最大成效和互惠互利的方式应用研究的互补专业知识。此次合作还将为夏威夷大学的学生和研究员提供充足的机会，让他们获得在这项研究工作中实施的基本神经科学技术的培训。拟议研究的结果将有助于了解 MHC 1 类限制性抗 HIV 特异性 CD8+ CTL 在控制中枢神经系统内 HIV-1 RNA 病毒载量中的作用，并将有助于了解 CSF HIV-1 之间的关系。 1 病毒载量与艾滋病痴呆症的发病机制。