CMV SPECIFIC CELLULAR IMMUNITY & REACTIVATION FOLLOWING SIV INFECTION IN RHESUS

CMV 特异性细胞免疫

• 批准号: 6453764
• 负责人: A KAUR
• 金额: $ 11.11万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6453764
• 关键词: AIDS; Mammalia; communicable diseases; immunology; 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 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

虽然巨细胞病毒是艾滋病的一种重要病原体，但相关资料很少