Discordance between frequency of human immunodeficiency virus type 1 (HIV-1)-specific gamma interferon-producing CD4+ T cells and HIV-1-specific lymphoproliferation in HIV-1-infected subjects with active viral replication
Discordance between frequency of human immunodeficiency virus type 1 (HIV-1)-specific gamma interferon-producing CD4+ T cells and HIV-1-specific lymphoproliferation in HIV-1-infected subjects with active viral replication
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DOI：
10.1128/jvi.76.12.5925-5936.2002
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发表时间：
2002-06-01
影响因子：
5.4
通讯作者：
Wilson, CC
中科院分区：
文献类型：
--
作者：
Palmer, BE;Boritz, E;Wilson, CC
不受控制的慢性人类免疫缺陷病毒1型（HIV-1）感染的一个标志是缺乏强烈的HIV-1特异性CD 4（+）T细胞增殖反应，但这种T辅助细胞（Th）缺陷的机制仍有争议。为了更好地了解HIV-1复制对Th细胞功能的影响，我们比较了体内病毒复制活跃的HIV-1感染受试者与接受抑制性高效抗逆转录病毒治疗（HAART）的受试者中，基于γ干扰素产生的CD 4（+）Th细胞应答与针对HIV-1蛋白的淋巴增殖应答的频率。尽管病毒载量和治疗状态存在差异，但在供体组之间，没有发现分泌麻黄碱的HIV-1特异性CD 4（+）T细胞的频率存在统计学显著差异。然而，HAART抑制受试者的HIV-1特异性淋巴增生反应显着高于病毒复制活跃的受试者。无论供体体内病毒载量如何，在用HIV-1抗原刺激的T细胞培养物中测得相似的HIV-1 RNA水平，但只有来自HAART抑制受试者的HIV-1特异性CD 4（+）T细胞在体外增殖，表明HIV-1体外复制并不排除HIV-1特异性淋巴细胞增殖。这项研究表明，在体内病毒持续复制的受试者中，HIV-1特异性CD 4（+）T细胞的频率和增殖能力之间存在不一致性，并表明体内HIV-1复制有助于观察到的HIV-1特异性CD 4（+）T细胞增殖缺陷。
One hallmark of uncontrolled, chronic human immunodeficiency virus type 1 (HIV-1) infection is the absence of strong HIV-1-specific, CD4(+) T-cell-proliferative responses, yet the mechanism underlying this T helper (Th)-cell defect remains controversial. To better understand the impact of HIV-1 replication on Th-cell function, we compared the frequency of CD4(+) Th-cell responses based on production of gamma interferon to lymphoproliferative responses directed against HIV-1 proteins in HIV-1-infected subjects with active in vivo viral replication versus those on suppressed highly active antiretroviral therapy (HAART). No statistically significant differences in the frequencies of cytokine-secreting, HIV-1-specific CD4(+) T cells between the donor groups were found, despite differences in viral load and treatment status. However, HIV-1-specific lymphoproliferative responses were significantly greater in the subjects with HAART suppression than in subjects with active viral replication. Similar levels of HIV-1 RNA were measured in T-cell cultures stimulated with HIV-1 antigens regardless of donor in vivo viral loads, but only HIV-1-specific CD4(+) T cells from subjects with HAART suppression proliferated in vitro, suggesting that HIV-1 replication in vitro does not preclude HIV-1-specific lymphoproliferation. This study demonstrates a discordance between the frequency and proliferative capacity of HIV-1-specific CD4(+) T cells in subjects with ongoing in vivo viral replication and suggests that in vivo HIV-1 replication contributes to the observed defect in HIV-1-specific CD4(+) T-cell proliferation.