Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo.
Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo.
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DOI：
10.1371/journal.pbio.0040090
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发表时间：
2006-04
期刊：
影响因子：
9.8
通讯作者：
McLean AR
中科院分区：
文献类型：
--
作者：
Asquith B;Edwards CT;Lipsitch M;McLean AR
了解细胞毒性T淋巴细胞(CTL)在控制HIV-1感染中的作用对疫苗设计至关重要。然而，很难评估CTL在自然感染中的重要性。不同的人类白细胞抗原(人类白细胞抗原)I类等位基因与不同的艾滋病进展速度相关，表明CTL起到保护作用。然而，在晚期HIV疾病患者中，抗逆转录病毒治疗后的病毒清除率并未受到影响，这表明CTL反应减弱不是疾病进展的主要潜在原因，CTL没有重要的保护作用。在这里，我们调和了这些明显相互矛盾的研究。我们估计了CTL反应施加的选择压力，这些CTL反应驱动了免疫逃逸变体的出现，从而直接量化了体内HIV-1特异性CTL的效率。我们估计，只有2%的高效感染的CD4+细胞死亡可归因于识别单个表位的CTL。我们认为，CTL每天杀死大量的感染细胞(约107)，但不是大多数感染细胞死亡的原因。尽管细胞毒性T淋巴细胞(CTL)每天杀死大量的HIV感染细胞，但它们可能不是大多数感染细胞死亡的原因。
Understanding the role of cytotoxic T lymphocytes (CTLs) in controlling HIV-1 infection is vital for vaccine design. However, it is difficult to assess the importance of CTLs in natural infection. Different human leukocyte antigen (HLA) class I alleles are associated with different rates of progression to AIDS, indicating that CTLs play a protective role. Yet virus clearance rates following antiretroviral therapy are not impaired in individuals with advanced HIV disease, suggesting that weakening of the CTL response is not the major underlying cause of disease progression and that CTLs do not have an important protective role. Here we reconcile these apparently conflicting studies. We estimate the selection pressure exerted by CTL responses that drive the emergence of immune escape variants, thereby directly quantifying the efficiency of HIV-1–specific CTLs in vivo. We estimate that only 2% of productively infected CD4 + cell death is attributable to CTLs recognising a single epitope. We suggest that CTLs kill a large number of infected cells (about 10 7) per day but are not responsible for the majority of infected cell death. Although cytotoxic T lymphocytes (CTLs) kill a large number of HIV-infected cells every day, they may not be responsible for the majority of infected cell death.
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HIV-1 GAG中的簇突变是逃避HLA-B27限制的细胞毒性T淋巴细胞反应所必需的。
影响因子：
15.3
作者：
Kelleher, A D;Long, C;Holmes, E C;Allen, R L;Wilson, J;Conlon, C;Workman, C;Shaunak, S;Olson, K;Goulder, P;Brander, C;Ogg, G;Sullivan, J S;Dyer, W;Jones, I;McMichael, A J;Rowland-Jones, S;Phillips, R E
通讯作者：
Phillips, R E
影响因子：
64.8
作者：
Goulder, PJR;Brander, C;Walker, BD
通讯作者：
Walker, BD
影响因子：
5.4
作者：
Geels, MJ;Cornelissen, M;Goudsmit, J
通讯作者：
Goudsmit, J
影响因子：
82.9
作者：
Goulder, PJR;Phillips, RE;RowlandJones, S
通讯作者：
RowlandJones, S
在慢性 HIV-1 感染中，针对改变的抗原处理的免疫选择导致细胞毒性 T 淋巴细胞逃逸。
影响因子：
15.3
作者：
Draenert, R;Le Gall, S;Pfafferott, KJ;Leslie, AJ;Chetty, P;Brander, C;Holmes, EC;Chang, SC;Feeney, ME;Addo, MM;Ruiz, LD;Ramduth, D;Jeena, P;Altfeld, M;Thomas, S;Tang, TH;Verrill, CL;Dixon, C;Prado, JG;Kiepiela, P;Martinez-Picado, J;Walker, BD;Goulder, PJR
通讯作者：
Goulder, PJR