Jacobson Mark A, Tan Qi Xuan, Girling Valerie, Poon C, Van Natta Mark, Jabs Douglas A, Inokuma Margaret, Maecker Holden T, Bredt Barry, Sinclair Elizabeth
Positive Health Program, Department of Medicine, University of California San Francisco, CA, USA.
Clin Infect Dis. 2008 Feb 1;46(3):458-66. doi: 10.1086/525853.
We examined the potential clinical utility of using a cytomegalovirus (CMV)-specific T cell immunoassay to determine the risk of developing new-onset CMV retinitis (CMVR) in patients with acquired immunodeficiency syndrome (AIDS).
CMV-specific T cell assays were performed by multiparameter flow cytometry using stored peripheral blood mononuclear cells that had been obtained in an observational study 2-6 months before new-onset CMVR was diagnosed in case patients (at a study visit during which a dilated ophthalmologic examination revealed no evidence of CMVR) and at the same study visit in control subjects (matched by absolute CD4(+) T cell count at entry) who did not subsequently develop retinitis during 1-6 years of study follow-up.
There were no significant differences in CMV-specific CD4(+) or CD8(+) T cell interferon-gamma or interleukin-2 expression in peripheral blood mononuclear cells from case patients and control subjects. Although there were trends toward lower percentages and absolute numbers of CMV-specific, cytokine-expressing CD8(+) T cells with a "late memory" phenotype (CD27(-)CD28(-)) as well as with an "early memory" phenotype (CD27(+)CD28(+)CD45RA(+)) in case patients than in control subjects, these differences were not statistically significant.
Many studies have reported that CMV-specific CD4(+) and CD8(+) T cell responses distinguish patients with active CMVR (i.e., who lack CMV-protective immunity) from those with inactive CMVR after immune restoration by antiretroviral treatment (i.e., who have CMV-protective immunity). However, the multiple CMV-specific immune responses we measured do not appear to have clinical utility for predicting the risk for patients with AIDS of developing new-onset CMVR with sufficient accuracy to be used in guiding therapeutic management.
我们研究了使用巨细胞病毒(CMV)特异性T细胞免疫测定法来确定获得性免疫缺陷综合征(AIDS)患者发生新发CMV视网膜炎(CMVR)风险的潜在临床效用。
通过多参数流式细胞术对储存的外周血单个核细胞进行CMV特异性T细胞测定,这些细胞是在一项观察性研究中获取的,在病例患者被诊断为新发CMVR前2 - 6个月(在一次研究访视中,散瞳眼科检查未发现CMVR证据)以及在对照受试者的同一研究访视时(根据入组时的绝对CD4(+) T细胞计数进行匹配)采集的,对照受试者在1 - 6年的研究随访期间未发生视网膜炎。
病例患者和对照受试者外周血单个核细胞中CMV特异性CD4(+)或CD8(+) T细胞干扰素 - γ或白细胞介素 - 2表达无显著差异。尽管病例患者中具有“晚期记忆”表型(CD27(-)CD28(-))以及“早期记忆”表型(CD27(+)CD28(+)CD45RA(+))的CMV特异性、表达细胞因子的CD8(+) T细胞的百分比和绝对数量有低于对照受试者的趋势,但这些差异无统计学意义。
许多研究报告称,CMV特异性CD4(+)和CD8(+) T细胞反应可区分活动性CMVR患者(即缺乏CMV保护性免疫的患者)与接受抗逆转录病毒治疗后免疫恢复的非活动性CMVR患者(即具有CMV保护性免疫的患者)。然而,我们测量的多种CMV特异性免疫反应似乎对预测AIDS患者发生新发CMVR的风险没有足够准确的临床效用,无法用于指导治疗管理。