Magnitude and Kinetics of CD8+ T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point.
Magnitude and Kinetics of CD8+ T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point.
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DOI：
10.1016/j.immuni.2015.08.012
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发表时间：
2015-09-15
期刊：
影响因子：
32.4
通讯作者：
Walker BD
中科院分区：
文献类型：
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作者：
Ndhlovu ZM;Kamya P;Mewalal N;Kløverpris HN;Nkosi T;Pretorius K;Laher F;Ogunshola F;Chopera D;Shekhar K;Ghebremichael M;Ismail N;Moodley A;Malik A;Leslie A;Goulder PJ;Buus S;Chakraborty A;Dong K;Ndung'u T;Walker BD
CD 8 + T细胞有助于控制HIV，但尚不清楚初始免疫应答是否调节病毒设定点。我们每周两次筛查高风险未感染女性的血浆HIV RNA，并确定了12种超急性感染。病毒血症的发作引发了大量的HIV特异性CD 8 + T细胞应答，非HIV记忆性CD 8 + T细胞的旁观者激活有限。HIV特异性CD 8 + T细胞分泌很少的干扰素-γ，经历快速凋亡并且未能上调白细胞介素7受体，已知白细胞介素7受体对T细胞存活很重要。达到峰值CD 8 + T细胞活化的速度和由病毒血症指数上升诱导的活化的绝对幅度与设定点病毒血症呈负相关。这些数据表明，快速，高强度的HIV诱导的CD 8 + T细胞反应是至关重要的后续免疫控制的急性感染，这对HIV疫苗的设计具有重要意义。
CD8+ T cells contribute to the control of HIV, but it is not clear whether initial immune responses modulate the viral set point. We screened high-risk uninfected women twice a week for plasma HIV RNA and identified twelve hyperacute infections. Onset of viremia elicited a massive HIV-specific CD8+ T cell response, with limited bystander activation of non-HIV memory CD8+ T cells. HIV-specific CD8+ T cells secreted little interferon-γ, underwent rapid apoptosis and failed to upregulate the interleukin 7 receptor, known to be important for T cell survival. The rapidity to peak CD8+ T cell activation and the absolute magnitude of activation induced by the exponential rise in viremia were inversely correlated with set point viremia. These data indicate that rapid, high magnitude HIV-induced CD8+ T cell responses are crucial for subsequent immune control of acute infection, which has important implications for HIV vaccine design.