Low CD4+ T-cell counts in HIV patients receiving effective antiretroviral therapy are associated with CD4+ T-cell activation and senescence but not with lower effector memory T-cell function
Low CD4+ T-cell counts in HIV patients receiving effective antiretroviral therapy are associated with CD4+ T-cell activation and senescence but not with lower effector memory T-cell function
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DOI：
10.1016/j.clim.2006.04.570
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发表时间：
2006-08-01
影响因子：
8.6
通讯作者：
French, Martyn A.
中科院分区：
文献类型：
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作者：
Fernandez, Sonia;Price, Patricia;French, Martyn A.
在接受长期有效ART的HIV-1患者中检测了免疫激活对CD 4（+）T细胞恢复的不利影响以及CD 4（+）T细胞计数和效应T细胞功能之间的关系。根据目前的CD 4（+）T细胞计数对ART治疗> 12个月和HIV RNA拷贝数< 50/ml> 6个月的患者进行分层，并对最低（n = 15）和最高（n = 12）三分位数的患者进行研究。我们通过流式细胞术评估增殖（Ki 67）、活化（HLA-DR、CD 38）和复制性衰老（CD 57），并通过IFN-γ ELISpot评估CD 4（+）T细胞对CMV的应答。表达HLA-DR或CD 57的CD 4（+）T细胞比例是总CD 4（+）T细胞计数（P = 0.0002和P = 0.002）和初始CD 4（+）T细胞计数（分别为P < 0.0001和P < 0.0001）的强单变量预测因子，表明CD 4（+）T细胞活化驱动初始CD 4（+）T细胞的消耗。这在胸腺较小/不可检测的患者中最明显。IFN-γ对CMV的反应在CD 4 + T细胞计数低或高的患者中相似。(c)2006年爱思唯尔公司All rights reserved.
The adverse effects of immune activation on CD4(+) T-cell recovery and the relationship between CD4(+) T-cell counts and effector T-cell function were examined in HIV-1 patients receiving tong-term effective ART. Patients with nadir CD4(+) T-cell counts < 100/mu l, > 12 months on ART and > 6 months with < 50 HIV RNA copies/ml were stratified by current CD4(+) T-cell counts and patients from the lowest (n = 15) and highest (n = 12) tertiles were studied. We assessed proliferation (Ki67), activation (HLA-DR, CD38) and replicative senescence (CD57) by flow cytometry and CD4(+) T-cell responses to CMV by IFN-gamma ELISpot. Proportions of CD4(+) T-cells expressing HLA-DR or CD57 were strong univariate predictors of total (P = 0.0002 and P = 0.002) and naive (P < 0.0001 and P < 0.0001, respectively) CD4(+) T-cell counts, suggesting that CD4(+) Tcell activation drives the depletion of naive CD4(+) T-cells. This was clearest in patients with a small/undetectable thymus. IFN-gamma responses to CMV were similar in patients with tow or high CD4(+) T-cell counts. (c) 2006 Elsevier Inc. All rights reserved.