Neuroimmune Modulation of Virus Immunity In Aging

衰老过程中病毒免疫的神经免疫调节

• 批准号: 6546363
• 负责人: Raymond Preston Stowe
• 金额: $ 4.21万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2004-02-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6546363
• 关键词: Epstein Barr virus; Herpesviridae disease; T lymphocyte; age difference; aging; cellular immunity; clinical research; cytotoxic T lymphocyte; developmental immunology; enzyme linked immunosorbent assay; flow cytometry; human middle age (35-64); human old age (65+); human subject; latent virus infection; neurohormones; neuroimmunomodulation; patient oriented research; questionnaires; stress; virus infection mechanism; virus load

This proposal is responsive to topic #I 1, Psychoneuroimmunology. Herpesviruses commonly establish infections in humans. These infections are usually characterized by an acute phase associated with minor morbidity and mortality followed by a chronic latent phase reflecting a balance between viral replication and the host immune response. Control over herpesvirus reactivation is primarily mediated by cellular immunity which declines with advancing age. As a result, herpesvirus infections are important pathogens in the elderly and result in considerable cost to the health care system. Another factor associated with herpesvirus reactivation is stress, and there has been considerable speculation linking stress and the appearance, duration, and intensity of herpesvirus infections. The immunological decrements associated with stress are of particular concern in the elderly because they already have age-related reductions in cellular immunity. Preliminary analysis of three elderly subjects has demonstrated lytic replication of Epstein-Barr virus (EBV), a member of the herpesvirus family. Therefore, the applicant will test the hypothesis that aging will decrease EBV-specific cellular immunity and increase reactivation of latent EBV. Furthermore, stress will result in higher viral load. Importantly, little is known about the immunobiology of EBV in aging. Studies outlined in this proposal will provide preliminary data regarding age-related declines in herpesvirus-specific T-cell immunity and subsequent latent virus reactivation. These data will subsequently be used to support an R01 application to develop a mechanistic investigation on how neuroendocrine hormones modulate herpesvirus-specific immunity in the elderly.

该提案响应主题#I 1，心理神经免疫学。疱疹病毒通常会引起人类感染。这些感染通常以发病率和死亡率较低的急性期为特征，随后是反映病毒复制和宿主免疫反应之间平衡的慢性潜伏期。对疱疹病毒再激活的控制主要是由细胞免疫介导的，细胞免疫随着年龄的增长而下降。因此，疱疹病毒感染是老年人的重要病原体，给医疗保健系统带来相当大的成本。与疱疹病毒重新激活相关的另一个因素是压力，并且有相当多的猜测将压力与疱疹病毒感染的出现、持续时间和强度联系起来。与压力相关的免疫衰退在老年人中尤其令人担忧，因为他们的细胞免疫力已经随着年龄的增长而下降。对三名老年受试者的初步分析表明，疱疹病毒家族的一员 Epstein-Barr 病毒 (EBV) 存在裂解性复制。因此，申请人将检验衰老会降低 EBV 特异性细胞免疫的假设 并增加潜伏 EBV 的重新激活。此外，压力会导致更高的病毒载量。重要的是，人们对 EBV 在衰老过程中的免疫生物学知之甚少。该提案中概述的研究将提供有关疱疹病毒特异性 T 细胞免疫力与年龄相关的下降以及随后的潜伏病毒重新激活的初步数据。这些数据随后将用于支持 R01 应用程序，以开展关于神经内分泌激素如何调节老年人疱疹病毒特异性免疫力的机制研究。