Prognostic value of HIV-1 Gag-specific CD4+ T-cell responses for progression to AIDS analyzed in a prospective cohort study
Prognostic value of HIV-1 Gag-specific CD4+ T-cell responses for progression to AIDS analyzed in a prospective cohort study
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DOI：
10.1182/blood-2005-07-2907
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发表时间：
2006-02-15
期刊：
影响因子：
20.3
通讯作者：
Miedema, F
中科院分区：
文献类型：
--
作者：
Jansen, CA;De Cuyper, IM;Miedema, F
HIV特异性CD4(+) t细胞反应与病毒控制之间的因果关系以及这些反应对HIV感染自然史的影响尚不清楚。在一项详细的纵向研究中，分析了长期无症状个体（LTA; n = 6）和艾滋病进展者（n = 7）的功能性HIV-1 gag特异性CD4(+) T细胞，中位随访时间分别为118个月和57个月。接下来，在一项前瞻性队列研究中测量了96名HIV感染者的HIV特异性CD4+ t辅助细胞反应，并使用Cox比例风险分析与临床终点相关。在详细的研究中，在感染早期观察到LTAs和进展者之间hiv特异性辅助细胞反应没有差异，但在感染晚期的进展者中，产生IL-2或IFN γ的gag特异性CD4(+) T细胞丢失。前瞻性队列研究中的多变量比例风险分析显示，血清转化后早期hiv特异性IL-2（+）、IFN γ(+)或IL-2(+)IFN γ (+) CD4(+) T细胞对进展为艾滋病的速度没有预后价值。我们的结果与病毒载量决定HIV特异性CD4(+) t细胞反应的性质和大小相一致，而不是HIV特异性CD4(+) t细胞反应控制HIV血浆病毒载量。
The causal relationship between HIV-specific CD4(+) T-cell responses and viral control and the effect of these responses on the natural history of HIV infection is unclear. In a detailed longitudinal study, functional HIV-1 Gag-specific CD4(+) T cells were analyzed in long-term asymptomatic individuals (LTA; n = 6) and progressors to AIDS (n = 7) with a median follow-up of, respectively, 118 and 57 months. Next, HIV-specific CD4+ T-helper cell responses were measured in a prospective cohort study among 96 HIV seroconverters and were related to clinical endpoints using Cox proportional hazard analyses. In the detailed study, no difference for HIV-specific helper-cell responses between LTAs and progressors was observed early in infection, but Gagspecific CD4(+) T cells producing IL-2 or IFN gamma were lost in progressors late in infection. Multivariate proportional hazard analyses in the prospective cohort study showed that HIV-specific IL-2(+), IFN gamma(+), or IL-2(+)IFN gamma(+) CD4(+) T cells early after seroconversion had no prognostic value for the rate of progression to AIDS. Our results are compatible with viral load determining the nature and magnitude of HIV-specific CD4(+) T-cell responses, rather than HIV-specific CD4(+) T-cell responses controlling HIV plasma viral load.