HLA class I-restricted T-cell responses may contribute to the control of human immunodeficiency virus infection, but such responses are not always necessary for long-term virus control
HLA class I-restricted T-cell responses may contribute to the control of human immunodeficiency virus infection, but such responses are not always necessary for long-term virus control
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DOI：
10.1128/jvi.02176-07
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发表时间：
2008-06-01
影响因子：
5.4
通讯作者：
Decks, Steven G.
中科院分区：
文献类型：
--
作者：
Emu, Brinda;Sinclair, Elizabeth;Decks, Steven G.
一种罕见的人类免疫缺陷病毒亚型(艾滋病毒感染者在不接受治疗的情况下保持检测不到的艾滋病毒RNA水平)(“精英控制者”)。为了阐明T细胞反应在介导病毒控制中的作用，我们在一大群精英控制者(HIV-RNA和75拷贝/毫升)、“病毒症”控制者(未经治疗的低水平病毒血症)、“非控制者”(高水平病毒血症)和“抗逆转录病毒治疗受抑”个体(抗逆转录病毒治疗中检测不到的HIV-RNA水平)中比较了人类白细胞抗原I类基因多态性和HIV特异性T细胞反应。精英和病毒控制者中产生干扰素和白介素2的CD_4(+)和CD_8(+)T细胞比例最高(P<；0.0001)。40%的精英控制者是人类白细胞抗原B*57，相比之下，病毒控制者只有23%，非控制者只有9%(P<；0.001)。其他在精英控制者中更常见的人类白细胞抗原I类等位基因包括：人类白细胞抗原-B*13、人类白细胞抗原-B*58和人类白细胞抗原-B*81(每种等位基因P<；0.05)。在精英控制组和病毒控制组中，携带保护性I类等位基因的患者产生GAG特异性CD8(+)T细胞的频率高于不携带这些等位基因的患者(P=0.01)。非控制者，无论有没有保护性等位基因，都有低水平的CD8(+)反应。因此，某些人类白细胞抗原I类等位基因在HIV控制者中富含，并与GAG特异性CD8(+)干扰素-γ+IL-2(+)T细胞相关。然而，在许多控制者中没有证据表明T细胞介导的控制，这表明在这些人中存在替代的病毒控制机制。在“非T细胞控制器”中定义病毒控制机制可能会导致对预防艾滋病毒传播或防止病毒复制的深入了解。
A rare subset of human immunodeficiency virus (HIV-infected individuals maintains undetectable HIV RNA levels without therapy ("elite controllers"). To clarify the role of T-cell responses in mediating virus control, we compared HLA class I polymorphisms and HIV-specific T-cell responses among a large cohort of elite controllers (HIV-RNA < 75 copies/ml), "viremic" controllers (low-level viremia without therapy), "non-controllers" (high-level viremia), and "antiretroviral therapy suppressed" individuals (undetectable HIV-RNA levels on antiretroviral therapy). The proportion of CD4(+) and CD8(+) T cells that produce gamma interferon (IFN-gamma) and interleukin-2 (IL-2) in response to Gag and Pol peptides was highest in the elite and viremic controllers (P < 0.0001). Forty percent of the elite controllers were HLA-B*57 compared to twenty-three percent of viremic controllers and nine percent of noncontrollers (P < 0.001). Other HLA class I alleles more common in elite controllers included HLA-B*13, HLA-B*58, and HILA-B*81 (P < 0.05 for each). Within elite and viremic controller groups, those with protective class I alleles had higher frequencies of Gag-specific CD8(+) T cells than those without these alleles (P = 0.01). Noncontrollers, with or without protective alleles, had low-level CD8(+) responses. Thus, certain HLA class I alleles are enriched in HIV controllers and are associated with strong Gag-specific CD8(+)IFN-gamma+IL-2(+) T cells. However, the absence of evidence of T cell-mediated control in many controllers suggests the presence of alternative mechanisms for viral control in these individuals. Defining mechanisms for virus control in "non-T-cell controllers" might lead to insights into preventing HIV transmission or preventing virus replication.