Adenovirus-specific human T cells are pervasive, polyfunctional, and cross-reactive.

Pre-existing immunity to adenovirus (Ad) reduces the efficacy of Ad-based vaccines. The goal of this study was to define the prevalence, magnitude, functionality and phenotype of Ad-specific human T cells directly ex vivo. To study the magnitude of T-cell responses to Ad, we developed a highly reproducible whole Ad vector stimulation assay for use with polychromatic flow cytometry. Ad-specific CD4+ and CD8+ T cell were detected in all 17 human subjects tested and were capable of proliferating upon restimulation. Ad-specific CD4+ T cells were primarily monofunctional CD4+ T cells that produced IL-2, IFN-γ or TNFα and expressed the memory markers CD27 and CD45RO. In contrast, Ad5-specific CD8+ T cells were more polyfunctional, expressing effector-like combinations of IFN-γ, MIP1α and perforin, and generally lacked CD27 and CD45RO expression. Ad-specific CD4+ and CD8+ T cell responses against chimpanzee-derived AdC6 and AdC7 were found in all subjects, indicating the commonality of cross-serotype reactivity of Ad-specific T cells. This cross-reactivity is due in part to extensive CD4+ and CD8+ T cell recognition of hexon regions conserved between multiple Ad serotypes. The prevalence, cross reactivity and effector like functions of Ad-specific T-cells in humans may affect the efficacy of Ad vector-based vaccines by eliminating vector infected cells even when rare serotype Ad vectors are employed.

预先存在的腺病毒（Ad）免疫会降低基于腺病毒的疫苗的效力。本研究的目的是直接在体外确定腺病毒特异性人类T细胞的患病率、数量、功能和表型。为了研究T细胞对腺病毒反应的程度，我们开发了一种高度可重复的全腺病毒载体刺激试验，用于多色流式细胞术。在所有17名接受测试的人类受试者中都检测到了腺病毒特异性CD4⁺和CD8⁺T细胞，并且它们在再次刺激时能够增殖。腺病毒特异性CD4⁺T细胞主要是产生IL - 2、IFN - γ或TNFα的单功能CD4⁺T细胞，并表达记忆标记CD27和CD45RO。相比之下，Ad5特异性CD8⁺T细胞具有更多的多功能性，表达IFN - γ、MIP1α和穿孔素等效应物样组合，并且通常缺乏CD27和CD45RO的表达。在所有受试者中都发现了针对黑猩猩来源的AdC6和AdC7的腺病毒特异性CD4⁺和CD8⁺T细胞反应，这表明腺病毒特异性T细胞的交叉血清型反应具有普遍性。这种交叉反应部分是由于多种腺病毒血清型之间保守的六邻体区域被广泛的CD4⁺和CD8⁺T细胞识别。人类中腺病毒特异性T细胞的患病率、交叉反应性和类似效应物的功能可能会通过清除被载体感染的细胞而影响基于腺病毒载体的疫苗的效力，即使使用了罕见血清型的腺病毒载体也是如此。