Adenoviral Vector Vaccination Induces a Conserved Program of CD8(+) T Cell Memory Differentiation in Mouse and Man.
Adenoviral Vector Vaccination Induces a Conserved Program of CD8(+) T Cell Memory Differentiation in Mouse and Man.
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DOI：
10.1016/j.celrep.2015.10.034
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发表时间：
2015-11-24
期刊：
影响因子：
8.8
通讯作者：
Klenerman P
中科院分区：
文献类型：
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作者：
Bolinger B;Sims S;Swadling L;O'Hara G;de Lara C;Baban D;Saghal N;Lee LN;Marchi E;Davis M;Newell E;Capone S;Folgori A;Barnes E;Klenerman P
在暴露于疫苗后，抗原特异性CD 8 + T细胞应答发展为长期记忆池。基于腺病毒载体的疫苗策略，例如，针对HCV开发的那些能够诱导和维持大量的CD 8 + T细胞群。这些群体在接种疫苗后如何进化仍有待于在转录水平上定义。我们解决了由编码模型抗原（β-半乳糖苷酶）的腺病毒载体诱导的趋异CD 8 + T细胞记忆池的转录调控。我们观察转录谱，模仿那些感染后的持久性病原体，鼠和人巨细胞病毒（CMV）。关键的转录标志包括归巢受体和抗凋亡途径的上调，由保守的转录因子网络驱动，包括T-bet。在人类中，腺病毒疫苗诱导类似的CMV样表型和转录因子调控。这些数据阐明了接种腺病毒载体后CD 8 + T细胞记忆的核心特征，并表明与持久性疱疹病毒共享的记忆发育的保守途径。腺载体疫苗接种诱导两种转录上不同的CD 8记忆应答。腺载体和CMV诱导的持续应答密切相关。小鼠和人的核心分子特征紧密共享。定义与腺病毒疫苗接种诱导的持续CD 8 + T细胞记忆相关的转录程序。他们将这些与持续性CMV感染后诱导的记忆“膨胀”有关。核心特征被发现是由小鼠和人共享的，包括TBX 21的突出作用。
Following exposure to vaccines, antigen-specific CD8+ T cell responses develop as long-term memory pools. Vaccine strategies based on adenoviral vectors, e.g., those developed for HCV, are able to induce and sustain substantial CD8+ T cell populations. How such populations evolve following vaccination remains to be defined at a transcriptional level. We addressed the transcriptional regulation of divergent CD8+ T cell memory pools induced by an adenovector encoding a model antigen (beta-galactosidase). We observe transcriptional profiles that mimic those following infection with persistent pathogens, murine and human cytomegalovirus (CMV). Key transcriptional hallmarks include upregulation of homing receptors and anti-apoptotic pathways, driven by conserved networks of transcription factors, including T-bet. In humans, an adenovirus vaccine induced similar CMV-like phenotypes and transcription factor regulation. These data clarify the core features of CD8+ T cell memory following vaccination with adenovectors and indicate a conserved pathway for memory development shared with persistent herpesviruses. Adenovector vaccination induces two transcriptionally distinct CD8 memory responses The sustained response induced by adenovectors and CMV is closely related The core molecular features are shared tightly in mouse and man Adenovaccines in humans induce a CD8 response that recapitulates these core features Bolinger et al. define the transcriptional program associated with sustained CD8+ T cell memory induced by adenoviral vaccination. They relate these to memory “inflation” induced following infection by persistent CMVs. Core features are found to be shared by mouse and man, including a prominent role for TBX21.