Evolution of CD8+ T cell immunity and viral escape following acute HIV-1 infection
Evolution of CD8+ T cell immunity and viral escape following acute HIV-1 infection
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DOI：
10.4049/jimmunol.171.7.3837
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发表时间：
2003-10-01
影响因子：
4.4
通讯作者：
McElrath, MJ
中科院分区：
文献类型：
--
作者：
Cao, JH;McNevin, J;McElrath, MJ
急性感染时HIV-1特异性CD 8（+）T细胞的诱导与病毒血症的减少有关CD 8（+）效应子在随后建立病毒设定点中的作用尚不清楚。为了解决这个问题，我们重点关注了两名具有相同初始Tat特异性CD 8（+）反应的急性感染患者，纵向分析了他们的CD 8（+）T细胞反应以及病毒载量和序列演变。在一名患者在急性感染期间开始治疗，Tat特异性CD 8（+）T细胞的频率逐渐减少，但持续存在，达特表位序列没有改变。相比之下，在第二个拒绝治疗的患者中，Tat特异性CD 8（+）T细胞消失到检测值以下，同时Gag特异性CD 4（+）T细胞丢失，因为血浆病毒血症达到设定点。这与达特表位内的逃逸变体和额外的Vpr表位的出现相一致。出现了新的CD 8（+）T细胞应答，但病毒血症没有进一步下降。这些发现表明，在没有治疗的情况下，最初的CD 8（+）T细胞应答对减少病毒血症的影响最大，而后来，不断演变的应答在进一步减少病毒载量方面的效率较低。结果还表明，T细胞的帮助可能有助于急性CD 8（+）T细胞反应的抗病毒效率。
Induction of HIV-1-specific CD8(+) T cells during acute infection is associated with a decline in viremia. The role CD8(+) effectors play in subsequently establishing viral set point remains unclear. To address this, we focused on two acutely infected patients with the same initial Tat-specific CD8(+) response, analyzing their CD8(+) T cell responses longitudinally in conjunction with viral load and sequence evolution. In one patient initiating treatment during acute infection, the frequencies of Tat-specific CD8(+) T cells gradually diminished but persisted, and the Tat epitope sequence was unaltered. By contrast, in the second patient who declined treatment, the Tat-specific CD8(+) T cells disappeared below detection, in conjunction with Gag-specific CD4(+) T cell loss, as plasma viremia reached a set point. This coincided with the emergence of an escape variant within the Tat epitope and an additional Vpr epitope. New CD8(+) T cell responses emerged but with no further associated decline in viremia. These findings indicate that, in the absence of treatment, the initial CD8(+) T cell responses have the greatest impact on reducing viremia, and that later, continuously evolving responses are less efficient in further reducing viral load. The results also suggest that T cell help may contribute to the antiviral efficiency of the acute CD8(+) T cell response.