Vaccine-Induced CD107a+ CD4+ T Cells Are Resistant to Depletion following AIDS Virus Infection
Vaccine-Induced CD107a+ CD4+ T Cells Are Resistant to Depletion following AIDS Virus Infection
复制标题
DOI：
10.1128/jvi.02032-14
复制
发表时间：
2014-10
影响因子：
5.4
通讯作者：
K. Terahara;Hiroshi Ishii;T. Nomura;N. Takahashi;A. Takeda;T. Shiino;Y. Tsunetsugu-Yokota;T. Matano
中科院分区：
文献类型：
--
作者：
K. Terahara;Hiroshi Ishii;T. Nomura;N. Takahashi;A. Takeda;T. Shiino;Y. Tsunetsugu-Yokota;T. Matano
病毒感染后，CD 4 + T细胞应答对于有效的抗体和CD 8 + T细胞诱导至关重要。然而，病毒特异性CD 4 + T细胞可以是人类免疫缺陷病毒（HIV）感染的优先靶点。因此，通过疫苗接种诱导HIV特异性CD 4 + T细胞可能导致感染后病毒复制增强。在本研究中，我们表明，疫苗诱导的表达CD 107 a的CD 4 + T细胞在猕猴艾滋病模型中对耗竭具有相对抗性。比较攻毒前和攻毒后1周接种疫苗的猕猴的CD 4 + T细胞中病毒特异性CD 107 a、巨噬细胞炎性蛋白-1 β、γ干扰素、肿瘤坏死因子α和白细胞介素-2应答，发现病毒暴露后CD 107 a −亚群显著减少，但CD 107 a+亚群未显著减少。那些未能控制病毒血症的疫苗接种者显示出更明显的减少，并且在第1周时表现出比未接种疫苗的动物显著更高的病毒载量。我们的研究结果表明，疫苗诱导的CD 107 a − CD 4 + T细胞在病毒感染后被耗尽，这表明在HIV疫苗设计中避免病毒特异性CD 107 a − CD 4 + T细胞诱导的基本原理。重要性诱导有效的抗体和/或CD 8 + T细胞应答是预防人类免疫缺陷病毒（HIV）感染的主要疫苗策略。CD 4 + T细胞应答对于有效的抗体和CD 8 + T细胞诱导至关重要。然而，病毒特异性CD 4 + T细胞可以是HIV感染的优先靶点。在这里，我们表明，疫苗诱导的病毒特异性CD 107 a − CD 4 + T细胞在感染猕猴艾滋病模型后大部分耗尽。虽然CD 4 + T细胞应答在病毒控制中很重要，但我们的研究结果表明，通过接种疫苗诱导病毒特异性CD 107 a − CD 4 + T细胞可能不会导致感染后有效的CD 4 + T细胞应答，而是有害的，并加速急性期的病毒复制。这表明HIV疫苗设计应避免病毒特异性CD 107 a − CD 4 + T细胞诱导。相反，这项研究发现，疫苗诱导的CD 107 a + CD 4 + T细胞对病毒攻击后的耗竭具有相对抗性，这意味着这些细胞的诱导可能是控制HIV的另一种方法。
ABSTRACT CD4+ T-cell responses are crucial for effective antibody and CD8+ T-cell induction following virus infection. However, virus-specific CD4+ T cells can be preferential targets for human immunodeficiency virus (HIV) infection. HIV-specific CD4+ T-cell induction by vaccination may thus result in enhancement of virus replication following infection. In the present study, we show that vaccine-elicited CD4+ T cells expressing CD107a are relatively resistant to depletion in a macaque AIDS model. Comparison of virus-specific CD107a, macrophage inflammatory protein-1β, gamma interferon, tumor necrosis factor alpha, and interleukin-2 responses in CD4+ T cells of vaccinated macaques prechallenge and 1 week postchallenge showed a significant reduction in the CD107a− but not the CD107a+ subset after virus exposure. Those vaccinees that failed to control viremia showed a more marked reduction and exhibited significantly higher viral loads at week 1 than unvaccinated animals. Our results indicate that vaccine-induced CD107a− CD4+ T cells are depleted following virus infection, suggesting a rationale for avoiding virus-specific CD107a− CD4+ T-cell induction in HIV vaccine design. IMPORTANCE Induction of effective antibody and/or CD8+ T-cell responses is a principal vaccine strategy against human immunodeficiency virus (HIV) infection. CD4+ T-cell responses are crucial for effective antibody and CD8+ T-cell induction. However, virus-specific CD4+ T cells can be preferential targets for HIV infection. Here, we show that vaccine-induced virus-specific CD107a− CD4+ T cells are largely depleted following infection in a macaque AIDS model. While CD4+ T-cell responses are important in viral control, our results indicate that virus-specific CD107a− CD4+ T-cell induction by vaccination may not lead to efficient CD4+ T-cell responses following infection but rather be detrimental and accelerate viral replication in the acute phase. This suggests that HIV vaccine design should avoid virus-specific CD107a− CD4+ T-cell induction. Conversely, this study found that vaccine-induced CD107a+ CD4+ T cells are relatively resistant to depletion following virus challenge, implying that induction of these cells may be an alternative approach toward HIV control.