Differential CD4+ T-Cell Cytokine and Cytotoxic Responses Between Reactivation and Latent Phases of Herpes Zoster Infection.
Differential CD4+ T-Cell Cytokine and Cytotoxic Responses Between Reactivation and Latent Phases of Herpes Zoster Infection.
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CD4+ T细胞是水痘带状疱疹病毒（VZV）有效免疫应答的关键组成部分，但它们在感染的急性期和潜伏期再激活期间的功能特性仍不清楚。在这里，我们使用多色流式细胞术和RNA测序技术评估了急性带状疱疹（HZ）患者外周血CD4+ T细胞的功能和转录组学特性，并与有HZ感染史的患者进行了比较。我们发现vzv特异性总记忆、效应记忆和中枢记忆CD4+ T细胞在急性HZ和先前HZ中的多功能性存在显著差异。与先前HZ患者相比，vzv特异性CD4+记忆t细胞反应在急性HZ再激活中具有更高的IFN-γ和IL-2产生细胞的频率。此外，vzv特异性CD4+ T细胞的细胞毒性标志物高于非vzv特异性细胞。来自这些个体的体外总记忆CD4+ T细胞转录组学分析显示，T细胞存活和分化途径的差异调节，包括TCR、细胞毒性T淋巴细胞（CTL）、T辅助细胞、炎症和MTOR信号通路。这些基因特征与IFN-γ和IL-2产生细胞响应VZV的频率相关。综上所述，来自急性HZ个体的vzv特异性CD4+ T细胞具有独特的功能和转录组特征，并且vzv特异性CD4+ T细胞作为一个群体具有更高的细胞毒性分子表达，包括穿孔素、颗粒酶- b和CD107a。
CD4+ T cells are a critical component of effective immune responses to varicella zoster virus (VZV), but their functional properties during the reactivation acute vs latent phase of infection remain poorly defined. Here we assessed the functional and transcriptomic properties of peripheral blood CD4+ T cells in persons with acute herpes zoster (HZ) compared to those with a prior history of HZ infection using multicolor flow cytometry and RNA sequencing. We found significant differences between the polyfunctionality of VZV-specific total memory, effector memory, and central memory CD4+ T cells in acute vs prior HZ. VZV-specific CD4+ memory T-cell responses in acute HZ reactivation had higher frequencies of IFN-γ and IL-2 producing cells compared to those with prior HZ. In addition, cytotoxic markers were higher in VZV-specific CD4+ T cells than non-VZV-specific cells. Transcriptomic analysis of ex vivo total memory CD4+ T cells from these individuals showed differential regulation of T-cell survival and differentiation pathways, including TCR, cytotoxic T lymphocytes (CTL), T helper, inflammation, and MTOR signaling pathways. These gene signatures correlated with the frequency of IFN-γ and IL-2 producing cells responding to VZV. In summary, VZV-specific CD4+ T cells from acute HZ individuals had unique functional and transcriptomic features, and VZV-specific CD4+ T cells as a group had a higher expression of cytotoxic molecules including Perforin, Granzyme-B, and CD107a.