CMV SPECIFIC CELLULAR IMMUNITY & REACTIVATION FOLLOWING SIV INFECTION IN RHESUS

尽管巨细胞病毒是艾滋病的重要病原体，但很少有人知道 关于HIV如何影响CMV或CMV是否以及如何加速的信息 SIV/猕猴模型在HIV感染过程中处于领先地位 艾滋病发病机制的动物模型，并允许检查 慢病毒与巨细胞病毒相互作用的对照实验 建立检测CMV特异性CTL的实验条件 巨细胞病毒特异性增殖前体的活性、定量 外周血中CMV病毒载量的检测 在巨细胞病毒血清阳性恒河猴中建立了QC-PCR 第I类MHC限制性和CD8+T淋巴细胞介导的CMV特异性CTL 在SIV幼稚巨细胞病毒血清阳性恒河猴中检测到反应 而在慢性SIV感染猕猴中，SIV病毒含量较低的猕猴 负载巨细胞病毒特异性增殖性T淋巴细胞的频率 前体在5,223人中有1人，2人中有1人在31,648人中 正常的巨细胞病毒血清阳性猕猴两只巨细胞病毒血清阳性， 肠道外感染SIVmac251的破伤风免疫恒河猴 正在进行纵向评估，以抑制CMV特异性和 召回抗原特异性免疫反应和巨细胞病毒再激活的深远意义 辅助性T细胞功能受到抑制，表现为45至115倍 巨细胞病毒特异性增殖性T细胞前体频率降低 淋巴细胞和前体频率下降3到20倍 破伤风特异性增殖性T淋巴细胞在第一个病例中很明显 在感染SIV两周后，并与一过性 黄褐色大衣CMV病毒DNA在辅助性T细胞中的丢失增加 在明显的外周CD4+T淋巴细胞减少之前就有功能存在 CMV特异性CTL活性在2周时下降，在4周和4周时消失 SIV感染后8周至SIV感染后8~12周， 尽管破伤风特异性增殖活性已经恢复到 基线或更高水平，CMV特异性增殖前体 令人惊讶的是，恢复到不到基线的20%， CMV特异性CTL活性在12周时明显恢复，即使在 CMV特异性辅助性T细胞不能完全恢复 功能阐明潜在的相互作用机制 CMV和SIV应有助于设计有效的抗病毒药物或 以免疫为基础的治疗策略控制发病率 艾滋病患者与巨细胞病毒感染的关系

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 rhes us m acaques 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 recover ed 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