CMV SPECIFIC CELLULAR IMMUNITY & CMV REACTIVATION FOLLOWING SIV INFECT IN RHESUS

CMV 特异性细胞免疫

• 批准号: 6277777
• 负责人: Amitinder Kaur
• 金额: $ 8.77万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277777
• 关键词: AIDS; Mammalia; Primates; immunology; infection; inflammation; lymphatic system; virus

Although CMV is an important pathogen in AIDS, little information is available on how HIV affects CMV or whether and how CMV accelerates the course of HIV infection. The SIV/macaque model is the leading animal model for AIDS pathogenesis and allows examination of the interactions between lentiviruses and CMV in a controlled experimental setting. Experimental conditions for detection of CMV-specific CTL activity, quantitation of CMV-specific proliferative precursor frequency and quantitation of CMV viral load in peripheral blood by QC-PCR were established in CMV-seropositive rhesus macaques. A vigorous class I MHC-restricted and CD8+ T lymphocyte-mediated CMV-specific CTL response was detected in SIV-naive CMV-seropositive rhesus macaques and in chronically SIV-infected rhesus macaques with low SIV viral loads. The frequency of CMV-specific proliferative T lymphocyte precursors ranged between one in 5,223 and one in 31,648 PBMC in two normal CMV-seropositive rhesus macaques. Two CMV-seropositive, tetanus-immunized rhesus macaques infected parenterally with SIVmac251 are being evaluated longitudinally for suppression of CMV-specific and recall antigen-specific immune responses and CMV reactivation. Profound suppression of T helper cell function as evidenced by a 45 to 115-fold decrease in precursor frequency of CMV-specific proliferative T lymphocytes and a 3 to 20-fold decrease in precursor frequency of tetanus-specific proliferative T lymphocytes was evident in the first two weeks after SIV infection and was associated with a transient increase in buffy coat CMV viral DNA. The loss in T helper cell function was present prior to marked peripheral CD4+ T lymphocytopenia. CMV-specific CTL activity was decreased at 2 weeks and absent at 4 and 8 weeks after SIV infection. By week 8 to 12 after SIV infection, though tetanus-specific proliferative activity had returned to baseline or greater levels, CMV-specific proliferative precursors had recovered to less than 20% of the baseline values. Surprisingly, recovery of CMV-specific CTL activity was evident at week 12, even in the absence of complete recovery of CMV-specific T helper cell function. The elucidation of mechanisms underlying interactions between CMV and SIV should help in the design of effective antiviral or immune-based therapeutic strategies to control the morbidity associated with CMV infection in AIDS.

虽然CMV是艾滋病的重要病原体，但有关CMV的信息很少。 艾滋病毒如何影响CMV或CMV是否以及如何加速 HIV感染的过程。 SIV/猕猴模型是 艾滋病发病机制的动物模型，并允许检查 慢病毒和CMV在对照实验中的相互作用 设置. CMV特异性CTL检测的实验条件 CMV特异性增殖前体的活性定量 外周血中CMV病毒载量的频率和定量， 在CMV血清阳性恒河猴中建立了QC-PCR。 一 强I类MHC限制性和CD 8 + T淋巴细胞介导 CMV特异性CTL反应在SIV初治CMV血清阳性的小鼠中检测到。 恒河猴和慢性SIV感染的恒河猴， SIV病毒载量低。 CMV特异性增殖性T细胞的频率 淋巴细胞前体细胞在5，223分之一至31，648分之一之间 两只正常CMV血清阳性恒河猴的PBMC。 两 CMV-血清阳性，破伤风免疫恒河猴感染 正在纵向评估SIVmac 251的胃肠外给药 CMV特异性和回忆抗原特异性免疫抑制 反应和CMV再激活。 严重抑制T辅助细胞 前体减少了45至115倍， CMV特异性增殖性T淋巴细胞的频率和3至 20-破伤风特异性抗体前体频率降低倍数 增殖性T淋巴细胞在治疗后的前两周明显增加， SIV感染与血沉棕黄色一过性增加有关 包被CMV病毒DNA。 辅助性T细胞功能丧失 在显著的外周CD 4 + T淋巴细胞减少症之前。 CMV特异性CTL 活动在2周时减少，在4周和8周时消失， SIV感染。 然而，在SIV感染后的第8至12周， 破伤风特异性增殖活性恢复至基线水平，或 更高的水平，CMV特异性增殖前体已恢复到 低于基线值的20%。 令人惊讶的是， CMV特异性CTL活性在第12周时是明显的，即使在没有 CMV特异性T辅助细胞功能的完全恢复。 的 阐明CMV和SIV之间相互作用的机制 应该有助于设计有效的抗病毒或基于免疫的 控制CMV相关发病率的治疗策略 感染艾滋病。